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This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 23 subunits (11 individual proteins ranging in size from 22 to 150 kD)[2]. Dynactin binds to cytoplasmic dynein, dynein cargo adaptors, and microtubules[3]. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis.
This subunit is commonly referred to p150-glued[1]. It is present in two copies per dynactin complex and forms an ~75nm long flexible arm that extends from the main body of dynactin[2]. The p150-glued arm contains binding sites for microtubules[4], the microtubule plus tip binding protein EB1[5], and the N-terminus of the dynein intermediate chain[6][7].
Alternative splicing of this gene results in at least 2 functionally distinct isoforms: a ubiquitously expressed one and a brain-specific one. Based on its cytogenetic location, this gene is considered as a candidate gene for limb-girdle muscular dystrophy.[8]
↑Berrueta L, Tirnauer JS, Schuyler SC, Pellman D, Bierer BE (April 1999). "The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain". Current Biology. 9 (8): 425–8. PMID10226031.
↑Karki S, Holzbaur EL (December 1995). "Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex". The Journal of Biological Chemistry. 270 (48): 28806–11. PMID7499404.
↑Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL (May 2004). "The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression". Nature Genetics. 36 (5): 462–70. doi:10.1038/ng1352. PMID15107855.
↑Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB (December 1996). "Identification of a novel 135-kDa Grb2-binding protein in osteoclasts". The Journal of Biological Chemistry. 271 (51): 33141–7. doi:10.1074/jbc.271.51.33141. PMID8955163.
↑Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr FA (October 2002). "The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes". Current Biology. 12 (20): 1792–5. doi:10.1016/s0960-9822(02)01221-6. PMID12401177.
Paschal BM, Holzbaur EL, Pfister KK, Clark S, Meyer DI, Vallee RB (July 1993). "Characterization of a 50-kDa polypeptide in cytoplasmic dynein preparations reveals a complex with p150GLUED and a novel actin". The Journal of Biological Chemistry. 268 (20): 15318–23. PMID8325901.
Holzbaur EL, Tokito MK (February 1996). "Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization". Genomics. 31 (3): 398–9. doi:10.1006/geno.1996.0068. PMID8838327.
Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB (December 1996). "Identification of a novel 135-kDa Grb2-binding protein in osteoclasts". The Journal of Biological Chemistry. 271 (51): 33141–7. doi:10.1074/jbc.271.51.33141. PMID8955163.
Blangy A, Arnaud L, Nigg EA (August 1997). "Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150". The Journal of Biological Chemistry. 272 (31): 19418–24. doi:10.1074/jbc.272.31.19418. PMID9235942.
Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Jockusch H, Schmitt-John T (July 1997). "Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases". Genomics. 43 (2): 242–4. doi:10.1006/geno.1997.4789. PMID9244444.
Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA (December 1997). "Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin". Human Molecular Genetics. 6 (13): 2205–12. doi:10.1093/hmg/6.13.2205. PMID9361024.
Li SH, Gutekunst CA, Hersch SM, Li XJ (February 1998). "Interaction of huntingtin-associated protein with dynactin P150Glued". The Journal of Neuroscience. 18 (4): 1261–9. PMID9454836.
Collin GB, Nishina PM, Marshall JD, Naggert JK (November 1998). "Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome". Genomics. 53 (3): 359–64. doi:10.1006/geno.1998.5542. PMID9799602.
Tokito MK, Holzbaur EL (November 1998). "The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B)". Biochimica et Biophysica Acta. 1442 (2–3): 432–6. doi:10.1016/S0167-4781(98)00195-X. PMID9805007.
Bingham JB, Schroer TA (February 1999). "Self-regulated polymerization of the actin-related protein Arp1". Current Biology. 9 (4): 223–6. doi:10.1016/S0960-9822(99)80095-5. PMID10074429.
Heimann K, Percival JM, Weinberger R, Gunning P, Stow JL (April 1999). "Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles". The Journal of Biological Chemistry. 274 (16): 10743–50. doi:10.1074/jbc.274.16.10743. PMID10196146.
Karki S, Tokito MK, Holzbaur EL (February 2000). "A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1". The Journal of Biological Chemistry. 275 (7): 4834–9. doi:10.1074/jbc.275.7.4834. PMID10671518.
Vancoillie G, Lambert J, Haeghen YV, Westbroek W, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P, Naeyaert JM (December 2000). "Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes". Pigment Cell Research. 13 (6): 449–57. doi:10.1034/j.1600-0749.2000.130607.x. PMID11153697.
