CX3CR1: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''CX3C chemokine receptor 1''' (CX3CR1) also known as the '''fractalkine receptor''' or '''G-protein coupled receptor 13''' (GPR13) is a [[protein]] that in humans is encoded by the ''CX3CR1'' [[gene]].<ref name="pmid7646814">{{cite journal | vauthors = Combadiere C, Ahuja SK, Murphy PM | title = Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene | journal = DNA and Cell Biology | volume = 14 | issue = 8 | pages = 673–80 | date = Aug 1995 | pmid = 7646814 | doi = 10.1089/dna.1995.14.673 }}</ref><ref name="pmid9726990">{{cite journal | vauthors = Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM | title = Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 37 | pages = 23799–804 | date = Sep 1998 | pmid = 9726990 | doi = 10.1074/jbc.273.37.23799 }}</ref>  As the name suggests, this receptor binds the chemokine [[CX3CL1]] (also called neurotactin or fractalkine).
'''CX3C chemokine receptor 1''' (CX3CR1) also known as the '''fractalkine receptor''' or '''G-protein coupled receptor 13''' (GPR13) is a [[protein]] that in humans is encoded by the ''CX3CR1'' [[gene]].<ref name="pmid7646814">{{cite journal | vauthors = Combadiere C, Ahuja SK, Murphy PM | title = Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene | journal = DNA and Cell Biology | volume = 14 | issue = 8 | pages = 673–80 | date = August 1995 | pmid = 7646814 | doi = 10.1089/dna.1995.14.673 }}</ref><ref name="pmid9726990">{{cite journal | vauthors = Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM | title = Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 37 | pages = 23799–804 | date = September 1998 | pmid = 9726990 | doi = 10.1074/jbc.273.37.23799 }}</ref>  As the name suggests, this receptor binds the chemokine [[CX3CL1]] (also called neurotactin or fractalkine).


== Function ==
== Function ==
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The fractalkine ligand CX3CL1 is a transmembrane protein and chemokine involved in the [[cell adhesion|adhesion]] and [[cell migration|migration]] of [[leukocyte]]s. The protein encoded by the CX3CR1 gene is a receptor for the fractalkine ligand.<ref name="entrez">{{cite web | title = Entrez Gene: chemokine (C-X3-C motif) receptor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1524| accessdate = }}</ref>
The fractalkine ligand CX3CL1 is a transmembrane protein and chemokine involved in the [[cell adhesion|adhesion]] and [[cell migration|migration]] of [[leukocyte]]s. The protein encoded by the CX3CR1 gene is a receptor for the fractalkine ligand.<ref name="entrez">{{cite web | title = Entrez Gene: chemokine (C-X3-C motif) receptor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1524| accessdate = }}</ref>


Expression of this receptor appears to be associated with [[lymphocytes]].<ref name="pmid9390561">{{cite journal | vauthors = Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O | title = Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion | journal = Cell | volume = 91 | issue = 4 | pages = 521–30 | date = Nov 1997 | pmid = 9390561 | doi = 10.1016/S0092-8674(00)80438-9 }}</ref> CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.<ref>{{cite journal|last1=Landsman|first1=L|last2=Bar-On|first2=L|last3=Zernecke|first3=A|last4=Kim|first4=KW|last5=Krauthgamer|first5=R|last6=Shagdarsuren|first6=E|last7=Lira|first7=SA|last8=Weissman|first8=IL|last9=Weber|first9=C|last10=Jung|first10=S|title=CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival.|journal=Blood|date=22 January 2009|volume=113|issue=4|pages=963-72|doi=10.1182/blood-2008-07-170787|pmid=18971423}}</ref>
Expression of this receptor appears to be associated with [[lymphocytes]].<ref name="pmid9390561">{{cite journal | vauthors = Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O | title = Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion | journal = Cell | volume = 91 | issue = 4 | pages = 521–30 | date = November 1997 | pmid = 9390561 | doi = 10.1016/S0092-8674(00)80438-9 }}</ref> CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.<ref>{{cite journal | vauthors = Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S | title = CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival | journal = Blood | volume = 113 | issue = 4 | pages = 963–72 | date = January 2009 | pmid = 18971423 | doi = 10.1182/blood-2008-07-170787 }}</ref>


Fractalkine signaling has also recently been discovered to play a developmental role in the migration of [[microglia]] in the [[central nervous system]] to their synaptic targets, where phagocytosis and synaptic refinement occur. CX3CR1 knockout mice had more synapses on cortical neurons than wild-type mice.{{Citation needed|date=March 2016}}
Fractalkine signaling has also recently been discovered to play a developmental role in the migration of [[microglia]] in the [[central nervous system]] to their synaptic targets, where phagocytosis and synaptic refinement occur. CX3CR1 knockout mice had more synapses on cortical neurons than wild-type mice.<ref>{{cite journal | vauthors = Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT | title = Synaptic pruning by microglia is necessary for normal brain development | language = en | journal = Science | volume = 333 | issue = 6048 | pages = 1456–8 | date = September 2011 | pmid = 21778362 | doi = 10.1126/science.1202529 }}</ref>


== Clinical significance ==
== Clinical significance ==


CX3CR1 also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to [[Subtypes_of_HIV#HIV-1|HIV-1]] infection and rapid progression to [[AIDS]].<ref name="entrez"/>  
CX3CR1 also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to [[Subtypes of HIV#HIV-1|HIV-1]] infection and rapid progression to [[AIDS]].<ref name="entrez"/>


CX3CR1 variants have been described to modify the survival time and the progression rate of patients with [[amyotrophic lateral sclerosis]].<ref>{{cite journal|last=Lopez-Lopez|first=Alan |author2=Gamez, Josep |author3=Syriani, Emilio |author4=Morales, Miguel |author5=Salvado, Maria |author6=Rodríguez, Manuel J. |author7=Mahy, Nicole |author8=Vidal-Taboada, Jose M. |title=CX3CR1 Is a Modifying Gene of Survival and Progression in Amyotrophic Lateral Sclerosis|journal=PLOS ONE|date=7 May 2014|doi=10.1371/journal.pone.0096528|url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0096528 |pmid=24806473 |pmc=4013026 |volume=9 |pages=e96528}}</ref>
CX3CR1 variants have been described to modify the survival time and the progression rate of patients with [[amyotrophic lateral sclerosis]].<ref>{{cite journal | vauthors = Lopez-Lopez A, Gamez J, Syriani E, Morales M, Salvado M, Rodríguez MJ, Mahy N, Vidal-Taboada JM | title = CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis | journal = PLOS One | volume = 9 | issue = 5 | pages = e96528 | date = 7 May 2014 | pmid = 24806473 | pmc = 4013026 | doi = 10.1371/journal.pone.0096528 }}</ref>


Mutations in CX3CR1 are associated to {{SWL|type=mutations_associated_to|target=dysplasia of the hip|label=dysplasia of the hip}}.<ref>{{cite journal | vauthors = Feldman GJ, Parvizi J, Sawan H, Erickson JA, Peters CL | title = Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family | journal = The Journal of Arthroplasty | volume = 29 | issue = 9 Suppl | pages = 238–41 | date = Sep 2014 | pmid = 24998320 | doi = 10.1016/j.arth.2014.05.014 }}</ref>
Mutations in CX3CR1 are associated to {{SWL|type=mutations_associated_to|target=dysplasia of the hip|label=dysplasia of the hip}}.<ref>{{cite journal | vauthors = Feldman GJ, Parvizi J, Sawan H, Erickson JA, Peters CL | title = Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family | journal = The Journal of Arthroplasty | volume = 29 | issue = 9 Suppl | pages = 238–41 | date = September 2014 | pmid = 24998320 | doi = 10.1016/j.arth.2014.05.014 }}</ref>
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== Further reading ==
== Further reading ==
{{Refbegin|33em}}
{{Refbegin|33em}}
* {{cite journal | vauthors = Robertson MJ | title = Role of chemokines in the biology of natural killer cells | journal = Journal of Leukocyte Biology | volume = 71 | issue = 2 | pages = 173–83 | date = Feb 2002 | pmid = 11818437 | doi =  }}
* {{cite journal | vauthors = Robertson MJ | title = Role of chemokines in the biology of natural killer cells | journal = Journal of Leukocyte Biology | volume = 71 | issue = 2 | pages = 173–83 | date = February 2002 | pmid = 11818437 | doi =  }}
* {{cite journal | vauthors = Raport CJ, Schweickart VL, Eddy RL, Shows TB, Gray PW | title = The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues | journal = Gene | volume = 163 | issue = 2 | pages = 295–9 | date = Oct 1995 | pmid = 7590284 | doi = 10.1016/0378-1119(95)00336-5 }}
* {{cite journal | vauthors = Raport CJ, Schweickart VL, Eddy RL, Shows TB, Gray PW | title = The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues | journal = Gene | volume = 163 | issue = 2 | pages = 295–9 | date = October 1995 | pmid = 7590284 | doi = 10.1016/0378-1119(95)00336-5 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Mizoue LS, Bazan JF, Johnson EC, Handel TM | title = Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1 | journal = Biochemistry | volume = 38 | issue = 5 | pages = 1402–14 | date = Feb 1999 | pmid = 9931005 | doi = 10.1021/bi9820614 }}
* {{cite journal | vauthors = Mizoue LS, Bazan JF, Johnson EC, Handel TM | title = Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1 | journal = Biochemistry | volume = 38 | issue = 5 | pages = 1402–14 | date = February 1999 | pmid = 9931005 | doi = 10.1021/bi9820614 }}
* {{cite journal | vauthors = Maho A, Bensimon A, Vassart G, Parmentier M | title = Mapping of the CCXCR1, CX3CR1, CCBP2 and CCR9 genes to the CCR cluster within the 3p21.3 region of the human genome | journal = Cytogenetics and Cell Genetics | volume = 87 | issue = 3-4 | pages = 265–8 | year = 2000 | pmid = 10702689 | doi = 10.1159/000015443 }}
* {{cite journal | vauthors = Maho A, Bensimon A, Vassart G, Parmentier M | title = Mapping of the CCXCR1, CX3CR1, CCBP2 and CCR9 genes to the CCR cluster within the 3p21.3 region of the human genome | journal = Cytogenetics and Cell Genetics | volume = 87 | issue = 3-4 | pages = 265–8 | year = 2000 | pmid = 10702689 | doi = 10.1159/000015443 }}
* {{cite journal | vauthors = Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debré P, Théodorou I, Combadière C | title = Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1 | journal = Science | volume = 287 | issue = 5461 | pages = 2274–7 | date = Mar 2000 | pmid = 10731151 | doi = 10.1126/science.287.5461.2274 }}
* {{cite journal | vauthors = Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debré P, Théodorou I, Combadière C | title = Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1 | journal = Science | volume = 287 | issue = 5461 | pages = 2274–7 | date = March 2000 | pmid = 10731151 | doi = 10.1126/science.287.5461.2274 }}
* {{cite journal | vauthors = Yoneda O, Imai T, Goda S, Inoue H, Yamauchi A, Okazaki T, Imai H, Yoshie O, Bloom ET, Domae N, Umehara H | title = Fractalkine-mediated endothelial cell injury by NK cells | journal = Journal of Immunology | volume = 164 | issue = 8 | pages = 4055–62 | date = Apr 2000 | pmid = 10754298 | doi = 10.4049/jimmunol.164.8.4055 }}
* {{cite journal | vauthors = Yoneda O, Imai T, Goda S, Inoue H, Yamauchi A, Okazaki T, Imai H, Yoshie O, Bloom ET, Domae N, Umehara H | title = Fractalkine-mediated endothelial cell injury by NK cells | journal = Journal of Immunology | volume = 164 | issue = 8 | pages = 4055–62 | date = April 2000 | pmid = 10754298 | doi = 10.4049/jimmunol.164.8.4055 }}
* {{cite journal | vauthors = Meucci O, Fatatis A, Simen AA, Miller RJ | title = Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 8075–80 | date = Jul 2000 | pmid = 10869418 | pmc = 16672 | doi = 10.1073/pnas.090017497 }}
* {{cite journal | vauthors = Meucci O, Fatatis A, Simen AA, Miller RJ | title = Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 8075–80 | date = July 2000 | pmid = 10869418 | pmc = 16672 | doi = 10.1073/pnas.090017497 }}
* {{cite journal | vauthors = Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, Gilfillan AM, Sassetti C, Metcalfe DD, Hwang ST | title = Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin | journal = European Journal of Immunology | volume = 30 | issue = 8 | pages = 2355–61 | date = Aug 2000 | pmid = 10940926 | doi = 10.1002/1521-4141(2000)30:8<2355::AID-IMMU2355>3.0.CO;2-# }}
* {{cite journal | vauthors = Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, Gilfillan AM, Sassetti C, Metcalfe DD, Hwang ST | title = Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin | journal = European Journal of Immunology | volume = 30 | issue = 8 | pages = 2355–61 | date = August 2000 | pmid = 10940926 | doi = 10.1002/1521-4141(2000)30:8<2355::AID-IMMU2355>3.0.CO;2-# }}
* {{cite journal | vauthors = Moatti D, Faure S, Fumeron F, El Walid Amara M, Seknadji P, McDermott DH, Debré P, Aumont MC, Murphy PM, de Prost D, Combadière C | title = Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease | journal = Blood | volume = 97 | issue = 7 | pages = 1925–8 | date = Apr 2001 | pmid = 11264153 | doi = 10.1182/blood.V97.7.1925 }}
* {{cite journal | vauthors = Moatti D, Faure S, Fumeron F, Amara M, Seknadji P, McDermott DH, Debré P, Aumont MC, Murphy PM, de Prost D, Combadière C | title = Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease | journal = Blood | volume = 97 | issue = 7 | pages = 1925–8 | date = April 2001 | pmid = 11264153 | doi = 10.1182/blood.V97.7.1925 }}
* {{cite journal | vauthors = Foussat A, Bouchet-Delbos L, Berrebi D, Durand-Gasselin I, Coulomb-L'Hermine A, Krzysiek R, Galanaud P, Levy Y, Emilie D | title = Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients | journal = Blood | volume = 98 | issue = 6 | pages = 1678–86 | date = Sep 2001 | pmid = 11535497 | doi = 10.1182/blood.V98.6.1678 }}
* {{cite journal | vauthors = Foussat A, Bouchet-Delbos L, Berrebi D, Durand-Gasselin I, Coulomb-L'Hermine A, Krzysiek R, Galanaud P, Levy Y, Emilie D | title = Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients | journal = Blood | volume = 98 | issue = 6 | pages = 1678–86 | date = September 2001 | pmid = 11535497 | doi = 10.1182/blood.V98.6.1678 }}
* {{cite journal | vauthors = Dichmann S, Herouy Y, Purlis D, Rheinen H, Gebicke-Härter P, Norgauer J | title = Fractalkine induces chemotaxis and actin polymerization in human dendritic cells | journal = Inflammation Research | volume = 50 | issue = 11 | pages = 529–33 | date = Nov 2001 | pmid = 11766992 | doi = 10.1007/PL00000230 }}
* {{cite journal | vauthors = Dichmann S, Herouy Y, Purlis D, Rheinen H, Gebicke-Härter P, Norgauer J | title = Fractalkine induces chemotaxis and actin polymerization in human dendritic cells | journal = Inflammation Research | volume = 50 | issue = 11 | pages = 529–33 | date = November 2001 | pmid = 11766992 | doi = 10.1007/PL00000230 }}
* {{cite journal | vauthors = Brand S, Sakaguchi T, Gu X, Colgan SP, Reinecker HC | title = Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells | journal = Gastroenterology | volume = 122 | issue = 1 | pages = 166–77 | date = Jan 2002 | pmid = 11781291 | doi = 10.1053/gast.2002.30329 }}
* {{cite journal | vauthors = Brand S, Sakaguchi T, Gu X, Colgan SP, Reinecker HC | title = Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells | journal = Gastroenterology | volume = 122 | issue = 1 | pages = 166–77 | date = January 2002 | pmid = 11781291 | doi = 10.1053/gast.2002.30329 }}
* {{cite journal | vauthors = Utaipat U, Duerr A, Rudolph DL, Yang C, Butera ST, Lupo D, Pisell T, Tangmunkongvorakul A, Kamtorn N, Nantachit N, Nagachinta T, Suriyanon V, Robison V, Nelson KE, Sittisombut N, Lal RB | title = Coreceptor utilization of HIV type 1 subtype E viral isolates from Thai men with HIV type 1-infected and uninfected wives | journal = AIDS Research and Human Retroviruses | volume = 18 | issue = 1 | pages = 1–11 | date = Jan 2002 | pmid = 11804551 | doi = 10.1089/088922202753394664 }}
* {{cite journal | vauthors = Utaipat U, Duerr A, Rudolph DL, Yang C, Butera ST, Lupo D, Pisell T, Tangmunkongvorakul A, Kamtorn N, Nantachit N, Nagachinta T, Suriyanon V, Robison V, Nelson KE, Sittisombut N, Lal RB | title = Coreceptor utilization of HIV type 1 subtype E viral isolates from Thai men with HIV type 1-infected and uninfected wives | journal = AIDS Research and Human Retroviruses | volume = 18 | issue = 1 | pages = 1–11 | date = January 2002 | pmid = 11804551 | doi = 10.1089/088922202753394664 }}
* {{cite journal | vauthors = Fong AM, Alam SM, Imai T, Haribabu B, Patel DD | title = CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19418–23 | date = May 2002 | pmid = 11909868 | doi = 10.1074/jbc.M201396200 }}
* {{cite journal | vauthors = Fong AM, Alam SM, Imai T, Haribabu B, Patel DD | title = CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19418–23 | date = May 2002 | pmid = 11909868 | doi = 10.1074/jbc.M201396200 }}
{{Refend}}
{{Refend}}

Latest revision as of 18:48, 6 January 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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CX3C chemokine receptor 1 (CX3CR1) also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13) is a protein that in humans is encoded by the CX3CR1 gene.[1][2] As the name suggests, this receptor binds the chemokine CX3CL1 (also called neurotactin or fractalkine).

Function

The fractalkine ligand CX3CL1 is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by the CX3CR1 gene is a receptor for the fractalkine ligand.[3]

Expression of this receptor appears to be associated with lymphocytes.[4] CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.[5]

Fractalkine signaling has also recently been discovered to play a developmental role in the migration of microglia in the central nervous system to their synaptic targets, where phagocytosis and synaptic refinement occur. CX3CR1 knockout mice had more synapses on cortical neurons than wild-type mice.[6]

Clinical significance

CX3CR1 also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS.[3]

CX3CR1 variants have been described to modify the survival time and the progression rate of patients with amyotrophic lateral sclerosis.[7]

Mutations in CX3CR1 are associated to dysplasia of the hip .[8]

References

  1. Combadiere C, Ahuja SK, Murphy PM (August 1995). "Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene". DNA and Cell Biology. 14 (8): 673–80. doi:10.1089/dna.1995.14.673. PMID 7646814.
  2. Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM (September 1998). "Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1". The Journal of Biological Chemistry. 273 (37): 23799–804. doi:10.1074/jbc.273.37.23799. PMID 9726990.
  3. 3.0 3.1 "Entrez Gene: chemokine (C-X3-C motif) receptor 1".
  4. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (November 1997). "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion". Cell. 91 (4): 521–30. doi:10.1016/S0092-8674(00)80438-9. PMID 9390561.
  5. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S (January 2009). "CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival". Blood. 113 (4): 963–72. doi:10.1182/blood-2008-07-170787. PMID 18971423.
  6. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (September 2011). "Synaptic pruning by microglia is necessary for normal brain development". Science. 333 (6048): 1456–8. doi:10.1126/science.1202529. PMID 21778362.
  7. Lopez-Lopez A, Gamez J, Syriani E, Morales M, Salvado M, Rodríguez MJ, Mahy N, Vidal-Taboada JM (7 May 2014). "CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis". PLOS One. 9 (5): e96528. doi:10.1371/journal.pone.0096528. PMC 4013026. PMID 24806473.
  8. Feldman GJ, Parvizi J, Sawan H, Erickson JA, Peters CL (September 2014). "Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family". The Journal of Arthroplasty. 29 (9 Suppl): 238–41. doi:10.1016/j.arth.2014.05.014. PMID 24998320.

Further reading

  • Robertson MJ (February 2002). "Role of chemokines in the biology of natural killer cells". Journal of Leukocyte Biology. 71 (2): 173–83. PMID 11818437.
  • Raport CJ, Schweickart VL, Eddy RL, Shows TB, Gray PW (October 1995). "The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues". Gene. 163 (2): 295–9. doi:10.1016/0378-1119(95)00336-5. PMID 7590284.
  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.