DCTN1 explained

Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.

Function

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).^[1] Dynactin binds to cytoplasmic dynein, dynein cargo adaptors, and microtubules.^[2] 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.^[3] It is present in two copies per dynactin complex and forms an ≈75 nm long flexible arm that extends from the main body of dynactin. 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]

Interactions

DCTN1 has been shown to interact with:

• BBS4,^[9]
• Dystonin,^[10]
• Grb2,^[11] and
• RAB6A.^[12]

Further reading

• Waterman-Storer CM, Karki S, Holzbaur EL . The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) . Proceedings of the National Academy of Sciences of the United States of America . 92 . 5 . 1634–8 . February 1995 . 7878030 . 42574 . 10.1073/pnas.92.5.1634 . 1995PNAS...92.1634W . free .
• Paschal BM, Holzbaur EL, Pfister KK, Clark S, Meyer DI, Vallee RB . 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 . July 1993 . 10.1016/S0021-9258(18)82472-3 . 8325901 . free .
• Vaughan KT, Vallee RB . Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued . The Journal of Cell Biology . 131 . 6 Pt 1 . 1507–16 . December 1995 . 8522607 . 2120689 . 10.1083/jcb.131.6.1507 .
• Holzbaur EL, Tokito MK . Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization . Genomics . 31 . 3 . 398–9 . February 1996 . 8838327 . 10.1006/geno.1996.0068 . free .
• Tokito MK, Howland DS, Lee VM, Holzbaur EL . Functionally distinct isoforms of dynactin are expressed in human neurons . Molecular Biology of the Cell . 7 . 8 . 1167–80 . August 1996 . 8856662 . 275970 . 10.1091/mbc.7.8.1167 .
• Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB . Identification of a novel 135-kDa Grb2-binding protein in osteoclasts . The Journal of Biological Chemistry . 271 . 51 . 33141–7 . December 1996 . 8955163 . 10.1074/jbc.271.51.33141 . free .
• Blangy A, Arnaud L, Nigg EA . 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 . August 1997 . 9235942 . 10.1074/jbc.272.31.19418 . free .
• Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Jockusch H, Schmitt-John T . Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases . Genomics . 43 . 2 . 242–4 . July 1997 . 9244444 . 10.1006/geno.1997.4789 .
• Waterman-Storer CM, Karki SB, Kuznetsov SA, Tabb JS, Weiss DG, Langford GM, Holzbaur EL . The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport . Proceedings of the National Academy of Sciences of the United States of America . 94 . 22 . 12180–5 . October 1997 . 9342383 . 23743 . 10.1073/pnas.94.22.12180 . 1997PNAS...9412180W . free .
• Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA . Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin . Human Molecular Genetics . 6 . 13 . 2205–12 . December 1997 . 9361024 . 10.1093/hmg/6.13.2205 . free .
• Li SH, Gutekunst CA, Hersch SM, Li XJ . Interaction of huntingtin-associated protein with dynactin P150Glued . The Journal of Neuroscience . 18 . 4 . 1261–9 . February 1998 . 9454836 . 6792727 . 10.1523/JNEUROSCI.18-04-01261.1998.
• Karki S, LaMonte B, Holzbaur EL . Characterization of the p22 subunit of dynactin reveals the localization of cytoplasmic dynein and dynactin to the midbody of dividing cells . The Journal of Cell Biology . 142 . 4 . 1023–34 . August 1998 . 9722614 . 2132867 . 10.1083/jcb.142.4.1023 .
• Collin GB, Nishina PM, Marshall JD, Naggert JK . Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome . Genomics . 53 . 3 . 359–64 . November 1998 . 9799602 . 10.1006/geno.1998.5542 .
• Tokito MK, Holzbaur EL . The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B) . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1442 . 2–3 . 432–6 . November 1998 . 9805007 . 10.1016/S0167-4781(98)00195-X . free .
• Bingham JB, Schroer TA . Self-regulated polymerization of the actin-related protein Arp1 . Current Biology . 9 . 4 . 223–6 . February 1999 . 10074429 . 10.1016/S0960-9822(99)80095-5 . 208851 . free . 1999CBio....9..223B .
• Heimann K, Percival JM, Weinberger R, Gunning P, Stow JL . Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles . The Journal of Biological Chemistry . 274 . 16 . 10743–50 . April 1999 . 10196146 . 10.1074/jbc.274.16.10743 . free .
• Eckley DM, Gill SR, Melkonian KA, Bingham JB, Goodson HV, Heuser JE, Schroer TA . Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end . The Journal of Cell Biology . 147 . 2 . 307–20 . October 1999 . 10525537 . 2174220 . 10.1083/jcb.147.2.307 .
• Karki S, Tokito MK, Holzbaur EL . A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1 . The Journal of Biological Chemistry . 275 . 7 . 4834–9 . February 2000 . 10671518 . 10.1074/jbc.275.7.4834 . free .
• Vancoillie G, Lambert J, Haeghen YV, Westbroek W, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P, Naeyaert JM . Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes . Pigment Cell Research . 13 . 6 . 449–57 . December 2000 . 11153697 . 10.1034/j.1600-0749.2000.130607.x . free .

External links

• GeneReviews/NIH/NCBI/UW entry on Perry syndrome

Notes and References

1. Urnavicius L, Zhang K, Diamant AG, Motz C, Schlager MA, Yu M, Patel NA, Robinson CV, Carter AP . The structure of the dynactin complex and its interaction with dynein . Science . 347 . 6229 . 1441–1446 . March 2015 . 25814576 . 4413427 . 10.1126/science.aaa4080 . 2015Sci...347.1441U .
2. Cianfrocco MA, DeSantis ME, Leschziner AE, Reck-Peterson SL . Mechanism and regulation of cytoplasmic dynein . Annual Review of Cell and Developmental Biology . 31 . 83–108 . 2015 . 26436706 . 4644480 . 10.1146/annurev-cellbio-100814-125438 .
3. Holzbaur EL, Hammarback JA, Paschal BM, Kravit NG, Pfister KK, Vallee RB . Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued . Nature . 351 . 6327 . 579–83 . June 1991 . 1828535 . 10.1038/351579a0 . 1991Natur.351..579H . 4263574 .
4. Waterman-Storer CM, Karki S, Holzbaur EL . The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) . Proceedings of the National Academy of Sciences of the United States of America . 92 . 5 . 1634–8 . February 1995 . 7878030 . 42574 . 10.1073/pnas.92.5.1634 . 1995PNAS...92.1634W . free .
5. Berrueta L, Tirnauer JS, Schuyler SC, Pellman D, Bierer BE . The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain . Current Biology . 9 . 8 . 425–8 . April 1999 . 10226031 . 10.1016/S0960-9822(99)80190-0 . 14191776 . free . 1999CBio....9..425B .
6. Karki S, Holzbaur EL . Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex . The Journal of Biological Chemistry . 270 . 48 . 28806–11 . December 1995 . 7499404 . 10.1074/jbc.270.48.28806 . free .
7. Vaughan KT, Vallee RB . Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued . The Journal of Cell Biology . 131 . 6 Pt 1 . 1507–16 . December 1995 . 8522607 . 2120689 . 10.1083/jcb.131.6.1507 .
8. Web site: Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila).
9. 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 . 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 . May 2004 . 15107855 . 10.1038/ng1352 . free .
10. Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, Wu C, Mobley W, Fuchs E, Yang Y . BPAG1n4 is essential for retrograde axonal transport in sensory neurons . The Journal of Cell Biology . 163 . 2 . 223–9 . October 2003 . 14581450 . 2173519 . 10.1083/jcb.200306075 .
11. Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB . Identification of a novel 135-kDa Grb2-binding protein in osteoclasts . The Journal of Biological Chemistry . 271 . 51 . 33141–7 . December 1996 . 8955163 . 10.1074/jbc.271.51.33141 . free .
12. Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr FA . The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes . Current Biology . 12 . 20 . 1792–5 . October 2002 . 12401177 . 10.1016/s0960-9822(02)01221-6 . 14031165 . free . 2002CBio...12.1792S .