Nucleoskeleton: Difference between revisions

Jump to navigation Jump to search
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
(5 intermediate revisions by 2 users not shown)
Line 4: Line 4:
The '''nucleoskeleton''' (NSK) provides a framework for [[DNA replication]], [[transcription]], [[chromatin remodeling]], [[Cell signaling|signaling]], and [[Messenger RNA|mRNA synthesis]], processing and transport.
The '''nucleoskeleton''' (NSK) provides a framework for [[DNA replication]], [[transcription]], [[chromatin remodeling]], [[Cell signaling|signaling]], and [[Messenger RNA|mRNA synthesis]], processing and transport.


=Introduction=
==Introduction==


Of the structures local to the [[nucleoplasm]], some serve to confine it such as the inner membrane of the [[nuclear envelope]]. While others are completely suspended within it, for example, the [[nucleolus]].
Of the structures local to the [[nucleoplasm]], some serve to confine it such as the inner membrane of the [[nuclear envelope]]. While others are completely suspended within it, for example, the [[nucleolus]].
Line 10: Line 10:
Other structural elements include the [[nuclear lamina]], core filaments, diffuse skeleton, nuclear bodies, the intranucleolar skeleton and [[Nucleolus#Fibrillar center (FC)|fibrillar center]]s.
Other structural elements include the [[nuclear lamina]], core filaments, diffuse skeleton, nuclear bodies, the intranucleolar skeleton and [[Nucleolus#Fibrillar center (FC)|fibrillar center]]s.


=Nuclear envelope membrane skeleton=
==Nuclear envelope membrane skeleton==


[[Emerin]] 18 kDa (no NLS) mediates inner nuclear membrane anchorage to the [[nuclear lamina]], regulates the flux of [[beta-catenin]] into the nucleus, and interacts with nuclear [[actin]].<ref name=emerin>{{ cite web |title=Entrez Gene: EMD emerin |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2010&ordinalpos=12&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref><ref name=EMD>{{ cite web |title=GENATLAS: GENE Database EMD |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref><ref name=EMERIN>{{ cite web |title=Apropos IpiRecord: IPI00032003 |url=http://apropos.mcw.edu/ipi_records/show/203523 }}</ref>
[[Emerin]] 18 kDa (no NLS) mediates inner nuclear membrane anchorage to the [[nuclear lamina]], regulates the flux of [[beta-catenin]] into the nucleus, and interacts with nuclear [[actin]].<ref name=emerin>{{ cite web |title=Entrez Gene: EMD emerin |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2010&ordinalpos=12&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref><ref name=EMD>{{ cite web |title=GENATLAS: GENE Database EMD |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref><ref name=EMERIN>{{ cite web |title=Apropos IpiRecord: IPI00032003 |url=http://apropos.mcw.edu/ipi_records/show/203523 }}</ref>


=[[Nuclear lamina]]=
[[Nesprin]] is a protein that is found in the outer nuclear membrane. It attaches to the actin filaments of the [[cytoskeleton]] and to emerin which is found in the inner nuclear membrane. Nesprin-1 is an isoform of [[enaptin]] which associates with the F-actin cytoskeleton and the nuclear membrane.<ref name=Padmakumar>{{ cite journal |author=Padmakumar VC, Abraham S, Braune S,  ''et al.'' |title=Enaptin, a giant actin-binding protein, is an element of the nuclear membrane and the actin cytoskeleton. |journal=Exp Cell Res. |volume=295 |issue= 2 |pages= 330-9 |year= 2004 |pmid= 15093733 }}</ref> Nesprin-2, like nesprin-1, is associated with actin-binding and nuclear envelope associated proteins.<ref name=Lüke>{{ cite journal |author=Lüke Y, Zaim H, Karakesisoglou I, Jaeger VM, ''et al.'' |title=Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin. |journal=J. Cell Sci. |volume=121 |issue= 11 |pages= 1887-98|year= 2008 |pmid= 18477613 }}</ref> Nesprin-2 is an important scaffold protein implicated in the maintenance of nuclear envelope architecture.
 
Nesprins have KASH [an acronym for Klarsicht, Anc-1, Syne Homology] domains which are conserved C-terminal protein regions of less than ~30 amino acids. KASH domains always follow a transmembrane domain and SUN [Sad1 and UNc (uncoordinated)-84 homology] domain proteins. In mammals, three KASH-domain proteins are represented, termed nesprin-1, -2 and -3. The C-terminal of the KASH domain contains a single transmembrane segment, followed by an evolutionarily conserved sequence (9–32 amino acids), located in the PNS ([[perinuclear space]]).<ref name=Schneider>{{ cite journal |author=Schneider M, Noegel A, Karakesisoglou I, |title=KASH-domain proteins and the cytoskeletal landscapes of the nuclear envelope. |journal=Biochem Soc Trans. |volume=36 |issue= 6 |pages= 1368-72|year= 2008 |pmid= 19021557 }}</ref> The KASH domain is necessary and sufficient for nuclear envelope (NE) targeting.
 
Most proteins containing [[KASH domains]] may be involved in the positioning of the nucleus in the cell. These domains may interact with proteins containing [[SUN domains]] in the space between the outer and inner nuclear membranes to bridge the [[nuclear envelope]] and transfer force from the nucleoskeleton to the [[cytoskeleton]]. Although KASH proteins probably localize to the outer nuclear membrane, some KASH protein isoforms may localize to the inner nuclear membrane.<ref name=Starr>{{cite journal |author=Starr DA, Fischer JA |title=KASH 'n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins |journal=Bioessays |volume=27 |issue=11 |pages=1136–46 |year=2005 |month=Nov |pmid=16237665 |doi=10.1002/bies.20312 }}</ref>
 
Like proteins containing KASH domains most proteins containing [[SUN domains]] may be involved in the positioning of the nucleus in the cell. SUN domains may interact directly with [[KASH domain]]s in the space between the outer and inner nuclear membranes to bridge the [[nuclear envelope]] and transfer force from the nucleoskeleton to the [[cytoskeleton]].  SUN proteins may preferentially localize to the inner nuclear membrane<ref name=Tzur>{{cite journal |author=Tzur YB, Wilson KL, Gruenbaum Y |title=SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton |journal=Nat Rev Mol Cell Biol. |volume=7 |issue=10 |pages=782–8 |year=2006 |month=Oct |pmid=16926857 |doi=10.1038/nrm2003 }}</ref>.
 
==[[Nuclear lamina]]==


The nuclear lamina is a dense, ~ 30 to 100 nanometers thick, fibrillar network composed of [[intermediate filament]]s made of [[lamin]] that lines the inner surface of the [[nuclear envelope]] in animal cells.
The nuclear lamina is a dense, ~ 30 to 100 nanometers thick, fibrillar network composed of [[intermediate filament]]s made of [[lamin]] that lines the inner surface of the [[nuclear envelope]] in animal cells.
Line 20: Line 28:
The [[nuclear pore complex]]es are embedded in the nuclear lamina.<ref name=Broers>{{ cite journal |author=Broers JL, Hutchison CJ, Ramaekers FC |title=Laminopathies | journal=J Pathol. |volume=204 |issue=4 |pages=478-88 |month=Nov |year=2004 |pmid=15495262 }}</ref>
The [[nuclear pore complex]]es are embedded in the nuclear lamina.<ref name=Broers>{{ cite journal |author=Broers JL, Hutchison CJ, Ramaekers FC |title=Laminopathies | journal=J Pathol. |volume=204 |issue=4 |pages=478-88 |month=Nov |year=2004 |pmid=15495262 }}</ref>


=[[Nuclear pore complex]]=
==[[Nuclear pore complex]]==


The nuclear pore complex restricts the size of particles including molecules that can get into the [[nucleoplasm]] to be incorporated into the nucleoskeleton. Larger proteins require a [[nuclear localization signal]] (NLS). The pores are 100 [[nm]] in total diameter, with an opening diameter of about 50 nm; however, the gap through which molecules freely diffuse is only about 9-10 nm wide,<ref name=Kramer>{{ cite journal |author=Kramer A, Ludwig Y, Shahin V, Oberleithner H |title=A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules |journal=J Biol Chem. |volume=282 |issue=43 |pages=31437-43 |month=Oct |year=2007 |doi=10.1074/jbc.M703720200 |pmid=17726020 |url=http://www.jbc.org/cgi/content/full/282/43/31437 }}</ref> due to the presence of regulatory systems within the center of the pore. The 10 nm diameter corresponds to an upper mass limit of 70 kDa.<ref name=Melchior>{{ cite journal |author=Melchior F, Gerace L |title=Mechanisms of nuclear protein import |journal=Curr Opin Cell Biol. |volume=7 |issue=3 |month=Jun |year=1995 |pages=310-8 |pmid=7662359 }}</ref>
The nuclear pore complex restricts the size of particles including molecules that can get into the [[nucleoplasm]] to be incorporated into the nucleoskeleton. Larger proteins require a [[nuclear localization signal]] (NLS). The pores are 100 [[nm]] in total diameter, with an opening diameter of about 50 nm; however, the gap through which molecules freely diffuse is only about 9-10 nm wide,<ref name=Kramer>{{ cite journal |author=Kramer A, Ludwig Y, Shahin V, Oberleithner H |title=A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules |journal=J Biol Chem. |volume=282 |issue=43 |pages=31437-43 |month=Oct |year=2007 |doi=10.1074/jbc.M703720200 |pmid=17726020 |url=http://www.jbc.org/cgi/content/full/282/43/31437 }}</ref> due to the presence of regulatory systems within the center of the pore. The 10 nm diameter corresponds to an upper mass limit of 70 kDa.<ref name=Melchior>{{ cite journal |author=Melchior F, Gerace L |title=Mechanisms of nuclear protein import |journal=Curr Opin Cell Biol. |volume=7 |issue=3 |month=Jun |year=1995 |pages=310-8 |pmid=7662359 }}</ref>
Line 28: Line 36:
The lamins of mammalian nuclei are polypeptides of 60-80 kDa: A (70 kDa), B (68 kDa), and C (60 kDa).<ref name=Urich>{{ cite book | author=Klaus Urich |title=Comparative Animal Biochemistry |publisher=Springer |year=1994 |page=359 |isbn=3540574204, 9783540574200 }}</ref> A- and B-type lamins, which form separate, but interacting, stable meshworks in the lamina, have different mobilities.<ref name=Shimi>{{ cite journal |author=Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T, Goldman RD |title=The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription |journal=Genes Dev. |volume=22 |issue=24 |pages=3409-21 |month=Dec |year=2008 |pmid=19141474 }}</ref> All of the lamins have a NLS.<ref name=LMN>{{ cite web |title=GENATLAS: Gene Database |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>
The lamins of mammalian nuclei are polypeptides of 60-80 kDa: A (70 kDa), B (68 kDa), and C (60 kDa).<ref name=Urich>{{ cite book | author=Klaus Urich |title=Comparative Animal Biochemistry |publisher=Springer |year=1994 |page=359 |isbn=3540574204, 9783540574200 }}</ref> A- and B-type lamins, which form separate, but interacting, stable meshworks in the lamina, have different mobilities.<ref name=Shimi>{{ cite journal |author=Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T, Goldman RD |title=The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription |journal=Genes Dev. |volume=22 |issue=24 |pages=3409-21 |month=Dec |year=2008 |pmid=19141474 }}</ref> All of the lamins have a NLS.<ref name=LMN>{{ cite web |title=GENATLAS: Gene Database |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>


=[[Actin]] nucleoskeleton=
==[[Actin]] nucleoskeleton==


Actins are highly conserved proteins that can form a tetramer. Further polymerization produces [[microfilament]]s such as those of the [[cytoskeleton]].  
Actins are highly conserved proteins that can form a tetramer. Further polymerization produces [[microfilament]]s such as those of the [[cytoskeleton]].  


==Nuclear actins==
===Nuclear actins===


Alpha actin: [[ACTA1]] 42 [[kDa]] is myosin binding and forms actin microfilaments, [[ACTA2]] 42 kDa is at least intracellular. As a part of nuclear actin, [[beta-actin]] (ACTB) has a 42 kDa mass as a monomer (no NLS), is a component of [[SWI/SNF]] chromatin remodeling complexes, and rapidly shuttles between the [[nucleohyaloplasm|nucleosol]] and [[cytosol]].<ref name=Olave>{{ cite journal |author=Olave IA, Reck-Peterson SL, Crabtree GR |title=Olave IA, Reck-Peterson SL, Crabtree GR |journal=Annu Rev Biochem. |volume=71 |pages=755-81 |year=2002 |pmid=12045110 }}</ref> Gamma actin: [[ACTC1]] 42 kDa is intracellular, incorporated into actin microfilaments, is dissolved in the cytosol.
Alpha actin: [[ACTA1]] 42 [[kDa]] is myosin binding and forms actin microfilaments, [[ACTA2]] 42 kDa is at least intracellular. As a part of nuclear actin, [[beta-actin]] (ACTB) has a 42 kDa mass as a monomer (no NLS), is a component of [[SWI/SNF]] chromatin remodeling complexes, and rapidly shuttles between the [[nucleohyaloplasm|nucleosol]] and [[cytosol]].<ref name=Olave>{{ cite journal |author=Olave IA, Reck-Peterson SL, Crabtree GR |title=Olave IA, Reck-Peterson SL, Crabtree GR |journal=Annu Rev Biochem. |volume=71 |pages=755-81 |year=2002 |pmid=12045110 }}</ref> Gamma actin: [[ACTC1]] 42 kDa is intracellular, incorporated into actin microfilaments, is dissolved in the cytosol.


==Nuclear actin-related proteins (ARPs)==
===Nuclear actin-related proteins (ARPs)===


The actin-related proteins (Arps) are also components of these chromatin remodeling complexes.<ref name=Olave/> [[ACTR1A]] 42.6 kDa is a subunit of dynactin, as is ACTR1B 42.3 kDa. Both subunits are Arp1 (centractin). Arp2 45 kDa<ref name=IPI00005159>{{ cite web |title=Apropos IpiRecord: IPI00005159 - ACTR2 |url=http://apropos.mcw.edu/ipi_records/show/196207 }}</ref> is a major constituent of the [[Arp2/3 complex]].<ref name=ACTR2>{{ cite web |title=Entrez Gene: ACTR2 ARP2 actin-related protein 2 homolog (yeast) |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10097&ordinalpos=9&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> Arp3 47 kDa<ref name=IPI00007068>{{ cite web |title=Apropos IpiRecord: IPI00007068 |url=http://apropos.mcw.edu/ipi_records/show/196766 }}</ref> is a major constituent of the Arp2/3 complex<ref name=ACTR3>{{ cite web |title=Entrez Gene: ACTR3 ARP3 actin-related protein 3 homolog |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10096&ordinalpos=10&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> which binds actin and may initiate nucleus assembly of actin.<ref name=Kelly>{{ cite journal |author=Kelly AE, Kranitz H, Dötsch V, Mullins RD |title=Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex |journal=J Biol Chem. |volum=281 |issue=15 |month=Apr |year=2006 |pages=10589-97 |pmid=16403731 }}</ref> Arp5 68 kDa<ref name=Arp5>{{ cite web |title=Human Protein Atlas ACTR5 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000101442 }}</ref> has no NLS but is involved in ATP-dependent chromatin remodeling.<ref name=ARP5-NPD>{{ cite web |title=Nuclear Protein Database ARP5 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP02151 }}</ref> Arp6 20 kDa and 36 kDa forms<ref name=IPI00171779>{{ cite web |title=Apropos IpiRecord: IPI00171779 |url=http://apropos.mcw.edu/ipi_records/show/208921 }}</ref> has nuclear localization<ref name=Ohfuchi>{{ cite journal |author=Ohfuchi E, Kato M, Sasaki M, Sugimoto K, Oma Y, Harata M |title=Vertebrate Arp6, a novel nuclear actin-related protein, interacts with heterochromatin protein 1 |journal=Eur J Cell Biol. |volume=85 |issue=5 |month=May |pages=411-21 |year=2006 |pmid=16487625 }}</ref>. Arp8 58 kDa<ref name=IPI00025646>{{ cite web |title=Apropos Ipirecord: IPI00025646 |url=http://apropos.mcw.edu/ipi_records/show/201870 }}</ref>, 37 kDa and 70 kDa<ref name=Q9H981>{{ cite web |title=Human Protein Atlas ACTR8 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000113812 }}</ref> chromosome associates<ref name=ACTR8>{{ cite web |title=Entrez Gene: ACTR8 ARP8 actin-related protein 8 homolog (yeast) |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=93973&ordinalpos=11&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> with involvement in chromatin remodelling (has NLS).<ref name=ARP8>{{ cite web |title=Nuclear Protein Database ARP8 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP02152 }}</ref> Arp10 46 kDa<ref name=hARP11>{{ cite web |title=Human Protein Atlas ACTR10 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000131966 }}</ref>. ArpM1 41 kDa<ref name=ARPM1-G>{{ cite web |title=GENATLAS : GENE Database ARPM1 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>. The Arp2/3 complex may be involved in the control of actin polymerization. ARPC1A 41 kDa is a subunit of the Arp2/3 complex along with ARPC1B 41 kDa, [[ARPC2]] 34 kDa, [[ARPC3]] 21 kDa, ARPC3B 21 kDa, [[ARPC4]] 20 kDa, [[ARPC5]] 16 kDa, and ARPC5L 17 kDa<ref name=ARPC5L-G>{{ cite web |title=GENATLAS : GENE Database ARPC5L |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>.
The actin-related proteins (Arps) are also components of these chromatin remodeling complexes.<ref name=Olave/> [[ACTR1A]] 42.6 kDa is a subunit of dynactin, as is ACTR1B 42.3 kDa. Both subunits are Arp1 (centractin). Arp2 45 kDa<ref name=IPI00005159>{{ cite web |title=Apropos IpiRecord: IPI00005159 - ACTR2 |url=http://apropos.mcw.edu/ipi_records/show/196207 }}</ref> is a major constituent of the [[Arp2/3 complex]].<ref name=ACTR2>{{ cite web |title=Entrez Gene: ACTR2 ARP2 actin-related protein 2 homolog (yeast) |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10097&ordinalpos=9&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> Arp3 47 kDa<ref name=IPI00007068>{{ cite web |title=Apropos IpiRecord: IPI00007068 |url=http://apropos.mcw.edu/ipi_records/show/196766 }}</ref> is a major constituent of the Arp2/3 complex<ref name=ACTR3>{{ cite web |title=Entrez Gene: ACTR3 ARP3 actin-related protein 3 homolog |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10096&ordinalpos=10&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> which binds actin and may initiate nucleus assembly of actin.<ref name=Kelly>{{ cite journal |author=Kelly AE, Kranitz H, Dötsch V, Mullins RD |title=Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex |journal=J Biol Chem. |volum=281 |issue=15 |month=Apr |year=2006 |pages=10589-97 |pmid=16403731 }}</ref> Arp5 68 kDa<ref name=Arp5>{{ cite web |title=Human Protein Atlas ACTR5 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000101442 }}</ref> has no NLS but is involved in ATP-dependent chromatin remodeling.<ref name=ARP5-NPD>{{ cite web |title=Nuclear Protein Database ARP5 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP02151 }}</ref> Arp6 20 kDa and 36 kDa forms<ref name=IPI00171779>{{ cite web |title=Apropos IpiRecord: IPI00171779 |url=http://apropos.mcw.edu/ipi_records/show/208921 }}</ref> has nuclear localization<ref name=Ohfuchi>{{ cite journal |author=Ohfuchi E, Kato M, Sasaki M, Sugimoto K, Oma Y, Harata M |title=Vertebrate Arp6, a novel nuclear actin-related protein, interacts with heterochromatin protein 1 |journal=Eur J Cell Biol. |volume=85 |issue=5 |month=May |pages=411-21 |year=2006 |pmid=16487625 }}</ref>. Arp8 58 kDa<ref name=IPI00025646>{{ cite web |title=Apropos Ipirecord: IPI00025646 |url=http://apropos.mcw.edu/ipi_records/show/201870 }}</ref>, 37 kDa and 70 kDa<ref name=Q9H981>{{ cite web |title=Human Protein Atlas ACTR8 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000113812 }}</ref> chromosome associates<ref name=ACTR8>{{ cite web |title=Entrez Gene: ACTR8 ARP8 actin-related protein 8 homolog (yeast) |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=93973&ordinalpos=11&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> with involvement in chromatin remodelling (has NLS).<ref name=ARP8>{{ cite web |title=Nuclear Protein Database ARP8 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP02152 }}</ref> Arp10 46 kDa<ref name=hARP11>{{ cite web |title=Human Protein Atlas ACTR10 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000131966 }}</ref>. ArpM1 41 kDa<ref name=ARPM1-G>{{ cite web |title=GENATLAS : GENE Database ARPM1 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>. The Arp2/3 complex may be involved in the control of actin polymerization. ARPC1A 41 kDa is a subunit of the Arp2/3 complex along with ARPC1B 41 kDa, [[ARPC2]] 34 kDa, [[ARPC3]] 21 kDa, ARPC3B 21 kDa, [[ARPC4]] 20 kDa, [[ARPC5]] 16 kDa, and ARPC5L 17 kDa<ref name=ARPC5L-G>{{ cite web |title=GENATLAS : GENE Database ARPC5L |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>.


==Nuclear actin-like proteins (ACTLs)==
===Nuclear actin-like proteins (ACTLs)===


Actin-like 6B (ACTL6B) is an Arp, a subunit of the BAF complex, which is functionally related to SWI/SNF complex, 47 kDa<ref name=BAF53B>{{ cite web |title=Human Protein Atlas ACTL6B gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000077080 }}</ref>, and has intracellular nucleus localization<ref name=ACTL6B-G>{{ cite web |title=GENATLAS : GENE Database ACTL6B |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>. As with ACTL6B, [[ACTL6A]] 53 kDa and 43 kDa (two different isoforms) binds chromatin, localizes to the nucleus, is involved in chromatin remodeling, and transcription.<ref name=BAF53A>{{ cite web |title=Human Protein Atlas ACTL6A gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000136518 }}</ref> It is a structural constituent of the nucleoskeleton.<ref name=ACTL6A-G>{{ cite web |title=GENATLAS : GENE Database ACTL6A |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> ACTRT1 42 kDa<ref name=Arp-T1>{{ cite web |title=Human Protein Atlas ACTRT1 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000123165 }}</ref>. ACTRT2 42 kDa<ref name=Arp-T2>{{ cite web |title=Human Protein Atlas ACTRT2 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000169717 }}</ref>.
Actin-like 6B (ACTL6B) is an Arp, a subunit of the BAF complex, which is functionally related to SWI/SNF complex, 47 kDa<ref name=BAF53B>{{ cite web |title=Human Protein Atlas ACTL6B gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000077080 }}</ref>, and has intracellular nucleus localization<ref name=ACTL6B-G>{{ cite web |title=GENATLAS : GENE Database ACTL6B |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>. As with ACTL6B, [[ACTL6A]] 53 kDa and 43 kDa (two different isoforms) binds chromatin, localizes to the nucleus, is involved in chromatin remodeling, and transcription.<ref name=BAF53A>{{ cite web |title=Human Protein Atlas ACTL6A gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000136518 }}</ref> It is a structural constituent of the nucleoskeleton.<ref name=ACTL6A-G>{{ cite web |title=GENATLAS : GENE Database ACTL6A |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> ACTRT1 42 kDa<ref name=Arp-T1>{{ cite web |title=Human Protein Atlas ACTRT1 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000123165 }}</ref>. ACTRT2 42 kDa<ref name=Arp-T2>{{ cite web |title=Human Protein Atlas ACTRT2 gene information |url=http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000169717 }}</ref>.


==Nuclear actin binding proteins (ABPs)==
===Nuclear actin binding proteins (ABPs)===


Supervillin ([[SVIL]]) has NLSs contained in its amino-terminus. The carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. SVIL is tightly associated with both actin filaments and plasma membranes,<ref name=Pestonjamasp>{{ cite journal |author=Pestonjamasp KN, Pope RK, Wulfkuhle JD, Luna EJ |title=Supervillin (p205): A novel membrane-associated, F-actin-binding protein in the villin/gelsolin superfamily. |journal=J. Cell Biol. |volume=139 |issue= 5 |pages= 1255-69 |year= 1997 |pmid= 9382871 |doi=  }}</ref> suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. Its function may include recruitment of actin and other cytoskeletal proteins into specialized structures at the plasma membrane and in the nuclei of growing cells.<ref name=supervillin>{{cite web | title = Entrez Gene: SVIL supervillin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6840| accessdate = }}</ref>
Supervillin ([[SVIL]]) has NLSs contained in its amino-terminus. The carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. SVIL is tightly associated with both actin filaments and plasma membranes,<ref name=Pestonjamasp>{{ cite journal |author=Pestonjamasp KN, Pope RK, Wulfkuhle JD, Luna EJ |title=Supervillin (p205): A novel membrane-associated, F-actin-binding protein in the villin/gelsolin superfamily. |journal=J. Cell Biol. |volume=139 |issue= 5 |pages= 1255-69 |year= 1997 |pmid= 9382871 |doi=  }}</ref> suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. Its function may include recruitment of actin and other cytoskeletal proteins into specialized structures at the plasma membrane and in the nuclei of growing cells.<ref name=supervillin>{{cite web | title = Entrez Gene: SVIL supervillin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6840| accessdate = }}</ref>
Line 52: Line 60:
One motor protein that localizes intracellularly to the nucleus is myosin 1F ({{Gene|MYO1F}}) 125 kDa.<ref name=MYO1F>{{ cite web |title=GENATLAS : GENE Database MYO1F |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> It does not have a NLS. Its N terminal motor domain uses ATP and has actin binding sites.<ref name=MYO1F/> The tail of MYO1F includes (1) a TH-1 region which may interact with membrane phospholipids, (2) a TH-2 proline-rich region which may contain an ATP-insensitive actin-binding site, and (3) a SH-3 domain found in a variety of cytoskeletal and signaling proteins.<ref name=Crozet>{{ cite journal |author=Crozet F, el Amraoui A, Blanchard S, Lenoir M, Ripoll C, Vago P, Hamel C, Fizames C, Levi-Acobas F, Depétris D, Mattei MG, Weil D, Pujol R, Petit C |title=Cloning of the genes encoding two murine and human cochlear unconventional type I myosins |journal=Genomics. |year=1997 |month=Mar |volume=40 |issue=2 |pages=332-41 |pmid=9119401 }}</ref>
One motor protein that localizes intracellularly to the nucleus is myosin 1F ({{Gene|MYO1F}}) 125 kDa.<ref name=MYO1F>{{ cite web |title=GENATLAS : GENE Database MYO1F |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> It does not have a NLS. Its N terminal motor domain uses ATP and has actin binding sites.<ref name=MYO1F/> The tail of MYO1F includes (1) a TH-1 region which may interact with membrane phospholipids, (2) a TH-2 proline-rich region which may contain an ATP-insensitive actin-binding site, and (3) a SH-3 domain found in a variety of cytoskeletal and signaling proteins.<ref name=Crozet>{{ cite journal |author=Crozet F, el Amraoui A, Blanchard S, Lenoir M, Ripoll C, Vago P, Hamel C, Fizames C, Levi-Acobas F, Depétris D, Mattei MG, Weil D, Pujol R, Petit C |title=Cloning of the genes encoding two murine and human cochlear unconventional type I myosins |journal=Genomics. |year=1997 |month=Mar |volume=40 |issue=2 |pages=332-41 |pmid=9119401 }}</ref>


=[[Nuclear matrix]]=
==[[Nuclear matrix]]==


Still others such as the [[nuclear matrix]]<ref name=Nickerson>{{cite journal |author=Nickerson J |title=Experimental observations of a nuclear matrix |journal=J. Cell. Sci. |volume=114 |issue=Pt 3 |pages=463–74 |year=2001 |month=February |pmid=11171316 |url=http://jcs.biologists.org/cgi/content/abstract/114/3/463}}</ref><ref name=Tetko>{{cite journal |author=Tetko IV, Haberer G, Rudd S, Meyers B, Mewes HW, Mayer KF |title=Spatiotemporal expression control correlates with intragenic scaffold matrix attachment regions (S/MARs) in Arabidopsis thaliana |journal=PLoS Comput. Biol. |volume=2 |issue=3 |pages=e21 |year=2006 |month=March |pmid=16604187 |pmc=1420657 |doi=10.1371/journal.pcbi.0020021 }}</ref> are found throughout the inside of the nucleus.
Still others such as the [[nuclear matrix]]<ref name=Nickerson>{{cite journal |author=Nickerson J |title=Experimental observations of a nuclear matrix |journal=J. Cell. Sci. |volume=114 |issue=Pt 3 |pages=463–74 |year=2001 |month=February |pmid=11171316 |url=http://jcs.biologists.org/cgi/content/abstract/114/3/463}}</ref><ref name=Tetko>{{cite journal |author=Tetko IV, Haberer G, Rudd S, Meyers B, Mewes HW, Mayer KF |title=Spatiotemporal expression control correlates with intragenic scaffold matrix attachment regions (S/MARs) in Arabidopsis thaliana |journal=PLoS Comput. Biol. |volume=2 |issue=3 |pages=e21 |year=2006 |month=March |pmid=16604187 |pmc=1420657 |doi=10.1371/journal.pcbi.0020021 }}</ref> are found throughout the inside of the nucleus.


=Nucleoplasmic veil=
==Nucleoplasmic veil==


Lamins within the nucleoplasm form another regular structure the nucleoplasmic veil<ref name=Goldman>{{cite journal | author = Goldman R, Gruenbaum Y, Moir R, Shumaker D, Spann T | title = Nuclear lamins: building blocks of nuclear architecture  | doi = 10.1101/gad.960502 | url=http://www.genesdev.org/cgi/content/full/16/5/533 | journal = Genes Dev | volume = 16 | issue = 5 | pages = 533–547 | year = 2002 | pmid = 11877373}}</ref>. The veil is excluded from the [[nucleolus]] and is present during [[interphase]].<ref name="Moir">{{cite  journal | author = Moir RD, Yoona M, Khuona S, Goldman RD. | title = Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells | journal = Journal of Cell Biology | year = 2000 | volume = 151 | issue = 6 | pages =  1155–1168 | pmid = 11121432 | doi = 10.1083/jcb.151.6.1155  }}</ref> The lamin structures that make up the veil bind [[chromatin]] and disrupting their structure inhibits transcription of protein-coding genes.<ref name=Spann>{{cite  journal  | author= Spann TP, Goldman AE, Wang C, Huang S, Goldman RD | journal = J of Cell Biol. | title = Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription | year = 2002 | volume = 156 | issue = 4 | pages = 603–608 | pmid = 11854306 | doi = 10.1083/jcb.200112047  }}</ref> Changes also occur in the lamina mesh size.<ref name=Shimi/>
Lamins within the nucleoplasm form another regular structure the nucleoplasmic veil<ref name=Goldman>{{cite journal | author = Goldman R, Gruenbaum Y, Moir R, Shumaker D, Spann T | title = Nuclear lamins: building blocks of nuclear architecture  | doi = 10.1101/gad.960502 | url=http://www.genesdev.org/cgi/content/full/16/5/533 | journal = Genes Dev | volume = 16 | issue = 5 | pages = 533–547 | year = 2002 | pmid = 11877373}}</ref>. The veil is excluded from the [[nucleolus]] and is present during [[interphase]].<ref name="Moir">{{cite  journal | author = Moir RD, Yoona M, Khuona S, Goldman RD. | title = Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells | journal = Journal of Cell Biology | year = 2000 | volume = 151 | issue = 6 | pages =  1155–1168 | pmid = 11121432 | doi = 10.1083/jcb.151.6.1155  }}</ref> The lamin structures that make up the veil bind [[chromatin]] and disrupting their structure inhibits transcription of protein-coding genes.<ref name=Spann>{{cite  journal  | author= Spann TP, Goldman AE, Wang C, Huang S, Goldman RD | journal = J of Cell Biol. | title = Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription | year = 2002 | volume = 156 | issue = 4 | pages = 603–608 | pmid = 11854306 | doi = 10.1083/jcb.200112047  }}</ref> Changes also occur in the lamina mesh size.<ref name=Shimi/>


=Intranuclear structures=
==Intranuclear structures==


In addition to forming the nuclear lamina, the lamins can form intranuclear structures.<ref name=Broers/>
In addition to forming the nuclear lamina, the lamins can form intranuclear structures.<ref name=Broers/>


=Microtubular structures=
==Microtubular structures==


Dynactin 1 (Dctn1) 150 kDa, the largest subunit of dynactin, which binds microtubules and is involved in chromosome movement, interacts with dynein.<ref name=DCTN1>{{ cite web |title=Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila) |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1639&ordinalpos=45&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> And, it has a NLS, is microtubule plus-end binding<ref name=DAP-150>{{ cite web |title=Nuclear Protein Database dynactin 1 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP00680 }}</ref>, has a second isoform of 135 kDa<ref name=IPI00029485>{{ cite web |title=Apropos IpiRecord: IPI00029485 - DCTN1, ISOFORM P150 OF DYNACTIN SUBUNIT 1 |url=http://apropos.mcw.edu/ipi_records/show/202889 }}</ref>, and binds to Arp1.<ref name=DCTN1-G>{{ cite web |title=GENATLAS : GENE Database DCTN1 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> Dynactin 2 (dynamitin) 50 kDa, 4-5 copies per dynactin molecule, is intracellular to the nucleus. Dynactin 3 22 kDa is a part of the dynactin complex, binding directly to Dctn1, and is intracellular to the nucleus<ref name=DCTN3-G>{{ cite web |title=GENATLAS : GENE Database DCTN3 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>. Dynactin 4 (Dctn4) 52 kDa is intracellular to the nucleus and a member of the pointed-end complex which contains Dctn4-6 and ACTR10.<ref name=DCTN4-G>{{ cite web |title=GENATLAS : GENE Database DCTN4 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> Dynactin 5 20 kDa and dynactin 6 21 kDa can easily localize to the nucleus.
Dynactin 1 (Dctn1) 150 kDa, the largest subunit of dynactin, which binds microtubules and is involved in chromosome movement, interacts with dynein.<ref name=DCTN1>{{ cite web |title=Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila) |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1639&ordinalpos=45&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref> And, it has a NLS, is microtubule plus-end binding<ref name=DAP-150>{{ cite web |title=Nuclear Protein Database dynactin 1 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP00680 }}</ref>, has a second isoform of 135 kDa<ref name=IPI00029485>{{ cite web |title=Apropos IpiRecord: IPI00029485 - DCTN1, ISOFORM P150 OF DYNACTIN SUBUNIT 1 |url=http://apropos.mcw.edu/ipi_records/show/202889 }}</ref>, and binds to Arp1.<ref name=DCTN1-G>{{ cite web |title=GENATLAS : GENE Database DCTN1 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> Dynactin 2 (dynamitin) 50 kDa, 4-5 copies per dynactin molecule, is intracellular to the nucleus. Dynactin 3 22 kDa is a part of the dynactin complex, binding directly to Dctn1, and is intracellular to the nucleus<ref name=DCTN3-G>{{ cite web |title=GENATLAS : GENE Database DCTN3 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref>. Dynactin 4 (Dctn4) 52 kDa is intracellular to the nucleus and a member of the pointed-end complex which contains Dctn4-6 and ACTR10.<ref name=DCTN4-G>{{ cite web |title=GENATLAS : GENE Database DCTN4 |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> Dynactin 5 20 kDa and dynactin 6 21 kDa can easily localize to the nucleus.
Line 70: Line 78:
The most common members of the tubulin family are α-tubulin ~55 kDa and β-tubulin ~55 kDa, both of which make up microtubules. Microtubules are assembled from heterodimers of one α- and one β-tubulin. β-tubulin has GTPase activity; i.e.,  hydrolyzes GTP to GDP whereas α-tubulin does not. [[Katanin]] is a heteromeric [[microtubule]]-severing protein. It contains a 60 kDa [[ATPase]] [[subunit]], which functions to sever microtubules. The second 80 kDa subunit regulates the activity of the ATPase and localizes the protein to the [[centrosomes]].<ref name=McNally>{{ cite journal |author=McNally FJ, Vale RD |title=Identification of katanin, an ATPase that severs and disassembles stable microtubules |journal=Cell. |year=1993 |month=Nov |volume=75 |issue=3 |pages=419-29 |pmid=8221885 }}</ref> Katanin forms 14–16 nm rings in its active [[oligomer|oligomerized]] state on the walls of microtubules.<ref name=Hartman>{{ cite journal |author=Hartman JJ, Mahr J, McNally K, Okawa K, Iwamatsu A, Thomas S, Cheesman S, Heuser J, Vale RD, McNally FJ |title=Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit |journal=Cell. |year=1998 |month=Apr |volume=93 |issue=2 |pages=277-87 |pmid=9568719 }}</ref> Even though katanin is brought into the nucleus, it does not act only in mitosis or meiosis. Katanin-mediated severing may serve to maintain organization by promoting microtubule disassembly, regulating their length for efficient movement, and releasing microtubules from the centrosome.<ref name=Ahmad>{{ cite journal |author=Ahmad FJ, Yu W, McNally FJ, Baas PW |title=An essential role for katanin in severing microtubules in the neuron |journal=J Cell Biol. |year=1999 |month=Apr |volume=145 |issue=2 |pages=305-15 }pmid=10209026 }}</ref>
The most common members of the tubulin family are α-tubulin ~55 kDa and β-tubulin ~55 kDa, both of which make up microtubules. Microtubules are assembled from heterodimers of one α- and one β-tubulin. β-tubulin has GTPase activity; i.e.,  hydrolyzes GTP to GDP whereas α-tubulin does not. [[Katanin]] is a heteromeric [[microtubule]]-severing protein. It contains a 60 kDa [[ATPase]] [[subunit]], which functions to sever microtubules. The second 80 kDa subunit regulates the activity of the ATPase and localizes the protein to the [[centrosomes]].<ref name=McNally>{{ cite journal |author=McNally FJ, Vale RD |title=Identification of katanin, an ATPase that severs and disassembles stable microtubules |journal=Cell. |year=1993 |month=Nov |volume=75 |issue=3 |pages=419-29 |pmid=8221885 }}</ref> Katanin forms 14–16 nm rings in its active [[oligomer|oligomerized]] state on the walls of microtubules.<ref name=Hartman>{{ cite journal |author=Hartman JJ, Mahr J, McNally K, Okawa K, Iwamatsu A, Thomas S, Cheesman S, Heuser J, Vale RD, McNally FJ |title=Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit |journal=Cell. |year=1998 |month=Apr |volume=93 |issue=2 |pages=277-87 |pmid=9568719 }}</ref> Even though katanin is brought into the nucleus, it does not act only in mitosis or meiosis. Katanin-mediated severing may serve to maintain organization by promoting microtubule disassembly, regulating their length for efficient movement, and releasing microtubules from the centrosome.<ref name=Ahmad>{{ cite journal |author=Ahmad FJ, Yu W, McNally FJ, Baas PW |title=An essential role for katanin in severing microtubules in the neuron |journal=J Cell Biol. |year=1999 |month=Apr |volume=145 |issue=2 |pages=305-15 }pmid=10209026 }}</ref>


=Nucleolar skeleton=
==Nucleolar skeleton==


Nucleolar skeletons are observable with light and electron microscopy and are characterized by ravels of filaments that are especially densely packed in the nucleolar cortex.<ref name=Franke>{{cite journal |author=Franke WW, Kleinschmidt JA, Spring H, Krohne G, Grund C, Trendelenburg MF, Stoehr M, Scheer U |title=A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis |month=Aug |journal=J Cell Biol. |year=1981 |volume=90 |issue=2 |pages=289-99 |pmid=2111883 }}</ref>
Nucleolar skeletons are observable with light and electron microscopy and are characterized by ravels of filaments that are especially densely packed in the nucleolar cortex.<ref name=Franke>{{cite journal |author=Franke WW, Kleinschmidt JA, Spring H, Krohne G, Grund C, Trendelenburg MF, Stoehr M, Scheer U |title=A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis |month=Aug |journal=J Cell Biol. |year=1981 |volume=90 |issue=2 |pages=289-99 |pmid=2111883 }}</ref>
Line 80: Line 88:
The skeleton contains considerable amounts of nuclear actin. The fibrillar meshworks indistinguishable from the nucleolar skeleton structure are also observable in anucleolate mutants, forming so-called “pseudo-nucleoli” suggesting that such skeletal proteins can assemble into spheroidal meshwork structures independent of the presence of nucleolar chromatin.<ref name=Franke/>
The skeleton contains considerable amounts of nuclear actin. The fibrillar meshworks indistinguishable from the nucleolar skeleton structure are also observable in anucleolate mutants, forming so-called “pseudo-nucleoli” suggesting that such skeletal proteins can assemble into spheroidal meshwork structures independent of the presence of nucleolar chromatin.<ref name=Franke/>


=Acknowledgements=
==Acknowledgements==


The content on this page was first contributed by: Henry A. Hoff.
The content on this page was first contributed by: Henry A. Hoff.
Line 86: Line 94:
Initial content for this page in some instances came from [http://www.wikipedia.org Wikipedia].
Initial content for this page in some instances came from [http://www.wikipedia.org Wikipedia].


=References=
==References==


{{reflist}}
{{reflist|2}}
 
==See also==
 
*[[Intermediate filaments]]
*[[Microfilaments]]
*[[Microtubules]]
*[[Nucleosol]]
*[[Nucleohyaloplasm]]
*[[Nucleoplasm]]
*[[Nuclear envelope]]
*[[Nucleolus]]
*[[Nuclear lamina]]
*[[Nuclear pore complex]]
*[[Cytoskeleton]]


{{Cytoskeletal Proteins}}
{{Cytoskeletal Proteins}}
{{Protein primary structure}}
{{Protein primary structure}}
{{Protein topics}}
{{Protein topics}}
{{SIB}}
 


[[Category:Cytoskeleton]]
[[Category:Cytoskeleton]]

Latest revision as of 20:11, 4 September 2012

WikiDoc Resources for Nucleoskeleton

Articles

Most recent articles on Nucleoskeleton

Most cited articles on Nucleoskeleton

Review articles on Nucleoskeleton

Articles on Nucleoskeleton in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Nucleoskeleton

Images of Nucleoskeleton

Photos of Nucleoskeleton

Podcasts & MP3s on Nucleoskeleton

Videos on Nucleoskeleton

Evidence Based Medicine

Cochrane Collaboration on Nucleoskeleton

Bandolier on Nucleoskeleton

TRIP on Nucleoskeleton

Clinical Trials

Ongoing Trials on Nucleoskeleton at Clinical Trials.gov

Trial results on Nucleoskeleton

Clinical Trials on Nucleoskeleton at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Nucleoskeleton

NICE Guidance on Nucleoskeleton

NHS PRODIGY Guidance

FDA on Nucleoskeleton

CDC on Nucleoskeleton

Books

Books on Nucleoskeleton

News

Nucleoskeleton in the news

Be alerted to news on Nucleoskeleton

News trends on Nucleoskeleton

Commentary

Blogs on Nucleoskeleton

Definitions

Definitions of Nucleoskeleton

Patient Resources / Community

Patient resources on Nucleoskeleton

Discussion groups on Nucleoskeleton

Patient Handouts on Nucleoskeleton

Directions to Hospitals Treating Nucleoskeleton

Risk calculators and risk factors for Nucleoskeleton

Healthcare Provider Resources

Symptoms of Nucleoskeleton

Causes & Risk Factors for Nucleoskeleton

Diagnostic studies for Nucleoskeleton

Treatment of Nucleoskeleton

Continuing Medical Education (CME)

CME Programs on Nucleoskeleton

International

Nucleoskeleton en Espanol

Nucleoskeleton en Francais

Business

Nucleoskeleton in the Marketplace

Patents on Nucleoskeleton

Experimental / Informatics

List of terms related to Nucleoskeleton

Editor-In-Chief: Henry A. Hoff

The nucleoskeleton (NSK) provides a framework for DNA replication, transcription, chromatin remodeling, signaling, and mRNA synthesis, processing and transport.

Introduction

Of the structures local to the nucleoplasm, some serve to confine it such as the inner membrane of the nuclear envelope. While others are completely suspended within it, for example, the nucleolus.

Other structural elements include the nuclear lamina, core filaments, diffuse skeleton, nuclear bodies, the intranucleolar skeleton and fibrillar centers.

Nuclear envelope membrane skeleton

Emerin 18 kDa (no NLS) mediates inner nuclear membrane anchorage to the nuclear lamina, regulates the flux of beta-catenin into the nucleus, and interacts with nuclear actin.[1][2][3]

Nesprin is a protein that is found in the outer nuclear membrane. It attaches to the actin filaments of the cytoskeleton and to emerin which is found in the inner nuclear membrane. Nesprin-1 is an isoform of enaptin which associates with the F-actin cytoskeleton and the nuclear membrane.[4] Nesprin-2, like nesprin-1, is associated with actin-binding and nuclear envelope associated proteins.[5] Nesprin-2 is an important scaffold protein implicated in the maintenance of nuclear envelope architecture.

Nesprins have KASH [an acronym for Klarsicht, Anc-1, Syne Homology] domains which are conserved C-terminal protein regions of less than ~30 amino acids. KASH domains always follow a transmembrane domain and SUN [Sad1 and UNc (uncoordinated)-84 homology] domain proteins. In mammals, three KASH-domain proteins are represented, termed nesprin-1, -2 and -3. The C-terminal of the KASH domain contains a single transmembrane segment, followed by an evolutionarily conserved sequence (9–32 amino acids), located in the PNS (perinuclear space).[6] The KASH domain is necessary and sufficient for nuclear envelope (NE) targeting.

Most proteins containing KASH domains may be involved in the positioning of the nucleus in the cell. These domains may interact with proteins containing SUN domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope and transfer force from the nucleoskeleton to the cytoskeleton. Although KASH proteins probably localize to the outer nuclear membrane, some KASH protein isoforms may localize to the inner nuclear membrane.[7]

Like proteins containing KASH domains most proteins containing SUN domains may be involved in the positioning of the nucleus in the cell. SUN domains may interact directly with KASH domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope and transfer force from the nucleoskeleton to the cytoskeleton. SUN proteins may preferentially localize to the inner nuclear membrane[8].

Nuclear lamina

The nuclear lamina is a dense, ~ 30 to 100 nanometers thick, fibrillar network composed of intermediate filaments made of lamin that lines the inner surface of the nuclear envelope in animal cells.

The nuclear pore complexes are embedded in the nuclear lamina.[9]

Nuclear pore complex

The nuclear pore complex restricts the size of particles including molecules that can get into the nucleoplasm to be incorporated into the nucleoskeleton. Larger proteins require a nuclear localization signal (NLS). The pores are 100 nm in total diameter, with an opening diameter of about 50 nm; however, the gap through which molecules freely diffuse is only about 9-10 nm wide,[10] due to the presence of regulatory systems within the center of the pore. The 10 nm diameter corresponds to an upper mass limit of 70 kDa.[11]

Due to the size limitation of the nuclear pore, these polypeptides would range from 9 kDa to <70 kDa and not need or have a NLS.

The lamins of mammalian nuclei are polypeptides of 60-80 kDa: A (70 kDa), B (68 kDa), and C (60 kDa).[12] A- and B-type lamins, which form separate, but interacting, stable meshworks in the lamina, have different mobilities.[13] All of the lamins have a NLS.[14]

Actin nucleoskeleton

Actins are highly conserved proteins that can form a tetramer. Further polymerization produces microfilaments such as those of the cytoskeleton.

Nuclear actins

Alpha actin: ACTA1 42 kDa is myosin binding and forms actin microfilaments, ACTA2 42 kDa is at least intracellular. As a part of nuclear actin, beta-actin (ACTB) has a 42 kDa mass as a monomer (no NLS), is a component of SWI/SNF chromatin remodeling complexes, and rapidly shuttles between the nucleosol and cytosol.[15] Gamma actin: ACTC1 42 kDa is intracellular, incorporated into actin microfilaments, is dissolved in the cytosol.

Nuclear actin-related proteins (ARPs)

The actin-related proteins (Arps) are also components of these chromatin remodeling complexes.[15] ACTR1A 42.6 kDa is a subunit of dynactin, as is ACTR1B 42.3 kDa. Both subunits are Arp1 (centractin). Arp2 45 kDa[16] is a major constituent of the Arp2/3 complex.[17] Arp3 47 kDa[18] is a major constituent of the Arp2/3 complex[19] which binds actin and may initiate nucleus assembly of actin.[20] Arp5 68 kDa[21] has no NLS but is involved in ATP-dependent chromatin remodeling.[22] Arp6 20 kDa and 36 kDa forms[23] has nuclear localization[24]. Arp8 58 kDa[25], 37 kDa and 70 kDa[26] chromosome associates[27] with involvement in chromatin remodelling (has NLS).[28] Arp10 46 kDa[29]. ArpM1 41 kDa[30]. The Arp2/3 complex may be involved in the control of actin polymerization. ARPC1A 41 kDa is a subunit of the Arp2/3 complex along with ARPC1B 41 kDa, ARPC2 34 kDa, ARPC3 21 kDa, ARPC3B 21 kDa, ARPC4 20 kDa, ARPC5 16 kDa, and ARPC5L 17 kDa[31].

Nuclear actin-like proteins (ACTLs)

Actin-like 6B (ACTL6B) is an Arp, a subunit of the BAF complex, which is functionally related to SWI/SNF complex, 47 kDa[32], and has intracellular nucleus localization[33]. As with ACTL6B, ACTL6A 53 kDa and 43 kDa (two different isoforms) binds chromatin, localizes to the nucleus, is involved in chromatin remodeling, and transcription.[34] It is a structural constituent of the nucleoskeleton.[35] ACTRT1 42 kDa[36]. ACTRT2 42 kDa[37].

Nuclear actin binding proteins (ABPs)

Supervillin (SVIL) has NLSs contained in its amino-terminus. The carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. SVIL is tightly associated with both actin filaments and plasma membranes,[38] suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. Its function may include recruitment of actin and other cytoskeletal proteins into specialized structures at the plasma membrane and in the nuclei of growing cells.[39]

SVIL is known to localize to chromosomes.[40] It also bundles F-actin.[41] And, binds myosin II which is not in the nucleus.[42]

One motor protein that localizes intracellularly to the nucleus is myosin 1F (MYO1F) 125 kDa.[43] It does not have a NLS. Its N terminal motor domain uses ATP and has actin binding sites.[43] The tail of MYO1F includes (1) a TH-1 region which may interact with membrane phospholipids, (2) a TH-2 proline-rich region which may contain an ATP-insensitive actin-binding site, and (3) a SH-3 domain found in a variety of cytoskeletal and signaling proteins.[44]

Nuclear matrix

Still others such as the nuclear matrix[45][46] are found throughout the inside of the nucleus.

Nucleoplasmic veil

Lamins within the nucleoplasm form another regular structure the nucleoplasmic veil[47]. The veil is excluded from the nucleolus and is present during interphase.[48] The lamin structures that make up the veil bind chromatin and disrupting their structure inhibits transcription of protein-coding genes.[49] Changes also occur in the lamina mesh size.[13]

Intranuclear structures

In addition to forming the nuclear lamina, the lamins can form intranuclear structures.[9]

Microtubular structures

Dynactin 1 (Dctn1) 150 kDa, the largest subunit of dynactin, which binds microtubules and is involved in chromosome movement, interacts with dynein.[50] And, it has a NLS, is microtubule plus-end binding[51], has a second isoform of 135 kDa[52], and binds to Arp1.[53] Dynactin 2 (dynamitin) 50 kDa, 4-5 copies per dynactin molecule, is intracellular to the nucleus. Dynactin 3 22 kDa is a part of the dynactin complex, binding directly to Dctn1, and is intracellular to the nucleus[54]. Dynactin 4 (Dctn4) 52 kDa is intracellular to the nucleus and a member of the pointed-end complex which contains Dctn4-6 and ACTR10.[55] Dynactin 5 20 kDa and dynactin 6 21 kDa can easily localize to the nucleus.

The most common members of the tubulin family are α-tubulin ~55 kDa and β-tubulin ~55 kDa, both of which make up microtubules. Microtubules are assembled from heterodimers of one α- and one β-tubulin. β-tubulin has GTPase activity; i.e., hydrolyzes GTP to GDP whereas α-tubulin does not. Katanin is a heteromeric microtubule-severing protein. It contains a 60 kDa ATPase subunit, which functions to sever microtubules. The second 80 kDa subunit regulates the activity of the ATPase and localizes the protein to the centrosomes.[56] Katanin forms 14–16 nm rings in its active oligomerized state on the walls of microtubules.[57] Even though katanin is brought into the nucleus, it does not act only in mitosis or meiosis. Katanin-mediated severing may serve to maintain organization by promoting microtubule disassembly, regulating their length for efficient movement, and releasing microtubules from the centrosome.[58]

Nucleolar skeleton

Nucleolar skeletons are observable with light and electron microscopy and are characterized by ravels of filaments that are especially densely packed in the nucleolar cortex.[59]

DNA as well as RNA are not constituents of this structure.

This insoluble protein filament complex may form a skeleton specific to the nucleolus proper that is different from other extraction-resistant components of the nucleus such as the matrix and lamina and is involved in the spatial organization of the nucleolar chromatin and its transcriptional products.[59] It is a framework of nucleolar filaments. The nucleolar skeletons are roughly spheroidal like the nucleolus itself and constitute the nucleolar cortex. The interior is formed by relatively loosely packed tangles of filaments ~4 nm thick arranged in higher-order coils of 30-40 nm dia. In the periphery are aggregates of various sizes representing local ravels of filament packing, with many filament continuities to internal filament elements.[59]

The skeleton contains considerable amounts of nuclear actin. The fibrillar meshworks indistinguishable from the nucleolar skeleton structure are also observable in anucleolate mutants, forming so-called “pseudo-nucleoli” suggesting that such skeletal proteins can assemble into spheroidal meshwork structures independent of the presence of nucleolar chromatin.[59]

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikipedia.

References

  1. "Entrez Gene: EMD emerin".
  2. "GENATLAS: GENE Database EMD".
  3. "Apropos IpiRecord: IPI00032003".
  4. Padmakumar VC, Abraham S, Braune S; et al. (2004). "Enaptin, a giant actin-binding protein, is an element of the nuclear membrane and the actin cytoskeleton". Exp Cell Res. 295 (2): 330–9. PMID 15093733.
  5. Lüke Y, Zaim H, Karakesisoglou I, Jaeger VM; et al. (2008). "Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin". J. Cell Sci. 121 (11): 1887–98. PMID 18477613.
  6. Schneider M, Noegel A, Karakesisoglou I, (2008). "KASH-domain proteins and the cytoskeletal landscapes of the nuclear envelope". Biochem Soc Trans. 36 (6): 1368–72. PMID 19021557.
  7. Starr DA, Fischer JA (2005). "KASH 'n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins". Bioessays. 27 (11): 1136–46. doi:10.1002/bies.20312. PMID 16237665. Unknown parameter |month= ignored (help)
  8. Tzur YB, Wilson KL, Gruenbaum Y (2006). "SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton". Nat Rev Mol Cell Biol. 7 (10): 782–8. doi:10.1038/nrm2003. PMID 16926857. Unknown parameter |month= ignored (help)
  9. 9.0 9.1 Broers JL, Hutchison CJ, Ramaekers FC (2004). "Laminopathies". J Pathol. 204 (4): 478–88. PMID 15495262. Unknown parameter |month= ignored (help)
  10. Kramer A, Ludwig Y, Shahin V, Oberleithner H (2007). "A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules". J Biol Chem. 282 (43): 31437–43. doi:10.1074/jbc.M703720200. PMID 17726020. Unknown parameter |month= ignored (help)
  11. Melchior F, Gerace L (1995). "Mechanisms of nuclear protein import". Curr Opin Cell Biol. 7 (3): 310–8. PMID 7662359. Unknown parameter |month= ignored (help)
  12. Klaus Urich (1994). Comparative Animal Biochemistry. Springer. p. 359. ISBN 3540574204, 9783540574200 Check |isbn= value: invalid character (help).
  13. 13.0 13.1 Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T, Goldman RD (2008). "The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription". Genes Dev. 22 (24): 3409–21. PMID 19141474. Unknown parameter |month= ignored (help)
  14. "GENATLAS: Gene Database".
  15. 15.0 15.1 Olave IA, Reck-Peterson SL, Crabtree GR (2002). "Olave IA, Reck-Peterson SL, Crabtree GR". Annu Rev Biochem. 71: 755–81. PMID 12045110.
  16. "Apropos IpiRecord: IPI00005159 - ACTR2".
  17. "Entrez Gene: ACTR2 ARP2 actin-related protein 2 homolog (yeast)".
  18. "Apropos IpiRecord: IPI00007068".
  19. "Entrez Gene: ACTR3 ARP3 actin-related protein 3 homolog".
  20. Kelly AE, Kranitz H, Dötsch V, Mullins RD (2006). "Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex". J Biol Chem. (15): 10589–97. PMID 16403731. Unknown parameter |month= ignored (help); Unknown parameter |volum= ignored (help)
  21. "Human Protein Atlas ACTR5 gene information".
  22. "Nuclear Protein Database ARP5".
  23. "Apropos IpiRecord: IPI00171779".
  24. Ohfuchi E, Kato M, Sasaki M, Sugimoto K, Oma Y, Harata M (2006). "Vertebrate Arp6, a novel nuclear actin-related protein, interacts with heterochromatin protein 1". Eur J Cell Biol. 85 (5): 411–21. PMID 16487625. Unknown parameter |month= ignored (help)
  25. "Apropos Ipirecord: IPI00025646".
  26. "Human Protein Atlas ACTR8 gene information".
  27. "Entrez Gene: ACTR8 ARP8 actin-related protein 8 homolog (yeast)".
  28. "Nuclear Protein Database ARP8".
  29. "Human Protein Atlas ACTR10 gene information".
  30. "GENATLAS : GENE Database ARPM1".
  31. "GENATLAS : GENE Database ARPC5L".
  32. "Human Protein Atlas ACTL6B gene information".
  33. "GENATLAS : GENE Database ACTL6B".
  34. "Human Protein Atlas ACTL6A gene information".
  35. "GENATLAS : GENE Database ACTL6A".
  36. "Human Protein Atlas ACTRT1 gene information".
  37. "Human Protein Atlas ACTRT2 gene information".
  38. Pestonjamasp KN, Pope RK, Wulfkuhle JD, Luna EJ (1997). "Supervillin (p205): A novel membrane-associated, F-actin-binding protein in the villin/gelsolin superfamily". J. Cell Biol. 139 (5): 1255–69. PMID 9382871.
  39. "Entrez Gene: SVIL supervillin".
  40. Pope RK, Pestonjamasp KN, Smith KP; et al. (1998). "Cloning, characterization, and chromosomal localization of human supervillin (SVIL)". Genomics. 52 (3): 342–51. PMID 9867483.
  41. Wulfkuhle JD, Donina IE, Stark NH; et al. (1999). "Domain analysis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals". J. Cell. Sci. 112 ( Pt 13): 2125–36. PMID 10362542.
  42. Chen Y, Takizawa N, Crowley JL; et al. (2003). "F-actin and myosin II binding domains in supervillin". J. Biol. Chem. 278 (46): 46094–106. doi:10.1074/jbc.M305311200. PMID 12917436.
  43. 43.0 43.1 "GENATLAS : GENE Database MYO1F".
  44. Crozet F, el Amraoui A, Blanchard S, Lenoir M, Ripoll C, Vago P, Hamel C, Fizames C, Levi-Acobas F, Depétris D, Mattei MG, Weil D, Pujol R, Petit C (1997). "Cloning of the genes encoding two murine and human cochlear unconventional type I myosins". Genomics. 40 (2): 332–41. PMID 9119401. Unknown parameter |month= ignored (help)
  45. Nickerson J (2001). "Experimental observations of a nuclear matrix". J. Cell. Sci. 114 (Pt 3): 463–74. PMID 11171316. Unknown parameter |month= ignored (help)
  46. Tetko IV, Haberer G, Rudd S, Meyers B, Mewes HW, Mayer KF (2006). "Spatiotemporal expression control correlates with intragenic scaffold matrix attachment regions (S/MARs) in Arabidopsis thaliana". PLoS Comput. Biol. 2 (3): e21. doi:10.1371/journal.pcbi.0020021. PMC 1420657. PMID 16604187. Unknown parameter |month= ignored (help)
  47. Goldman R, Gruenbaum Y, Moir R, Shumaker D, Spann T (2002). "Nuclear lamins: building blocks of nuclear architecture". Genes Dev. 16 (5): 533–547. doi:10.1101/gad.960502. PMID 11877373.
  48. Moir RD, Yoona M, Khuona S, Goldman RD. (2000). "Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells". Journal of Cell Biology. 151 (6): 1155–1168. doi:10.1083/jcb.151.6.1155. PMID 11121432.
  49. Spann TP, Goldman AE, Wang C, Huang S, Goldman RD (2002). "Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription". J of Cell Biol. 156 (4): 603–608. doi:10.1083/jcb.200112047. PMID 11854306.
  50. "Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)".
  51. "Nuclear Protein Database dynactin 1".
  52. "Apropos IpiRecord: IPI00029485 - DCTN1, ISOFORM P150 OF DYNACTIN SUBUNIT 1".
  53. "GENATLAS : GENE Database DCTN1".
  54. "GENATLAS : GENE Database DCTN3".
  55. "GENATLAS : GENE Database DCTN4".
  56. McNally FJ, Vale RD (1993). "Identification of katanin, an ATPase that severs and disassembles stable microtubules". Cell. 75 (3): 419–29. PMID 8221885. Unknown parameter |month= ignored (help)
  57. Hartman JJ, Mahr J, McNally K, Okawa K, Iwamatsu A, Thomas S, Cheesman S, Heuser J, Vale RD, McNally FJ (1998). "Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit". Cell. 93 (2): 277–87. PMID 9568719. Unknown parameter |month= ignored (help)
  58. Ahmad FJ, Yu W, McNally FJ, Baas PW (1999). "An essential role for katanin in severing microtubules in the neuron". J Cell Biol. 145 (2): 305-15 }pmid=10209026. Unknown parameter |month= ignored (help)
  59. 59.0 59.1 59.2 59.3 Franke WW, Kleinschmidt JA, Spring H, Krohne G, Grund C, Trendelenburg MF, Stoehr M, Scheer U (1981). "A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis". J Cell Biol. 90 (2): 289–99. PMID 2111883. Unknown parameter |month= ignored (help)

See also

Template:WH Template:WS