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词条 DCTN1
释义

  1. Function

  2. Interactions

  3. References

  4. Further reading

  5. External links

{{Infobox_gene}}Dynactin subunit 1 is a protein that in humans is encoded by the DCTN1 gene.[1]

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 ~75nm long flexible arm that extends from the main body of dynactin[1]. 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]

References

1. ^{{cite journal | vauthors = Urnavicius L, Zhang K, Diamant AG, Motz C, Schlager MA, Yu M, Patel NA, Robinson CV, Carter AP | title = The structure of the dynactin complex and its interaction with dynein | journal = Science | volume = 347 | issue = 6229 | pages = 1441–1446 | date = March 2015 | pmid = 25814576 | pmc = 4413427 | doi = 10.1126/science.aaa4080 }}
2. ^{{cite journal | vauthors = Cianfrocco MA, DeSantis ME, Leschziner AE, Reck-Peterson SL | title = Mechanism and regulation of cytoplasmic dynein | journal = Annual Review of Cell and Developmental Biology | volume = 31 | pages = 83–108 | date = 2015 | pmid = 26436706 | pmc = 4644480 | doi = 10.1146/annurev-cellbio-100814-125438 }}
3. ^{{cite journal | vauthors = Holzbaur EL, Hammarback JA, Paschal BM, Kravit NG, Pfister KK, Vallee RB | title = Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued | journal = Nature | volume = 351 | issue = 6327 | pages = 579–83 | date = June 1991 | pmid = 1828535 | pmc = | doi = 10.1038/351579a0 }}
4. ^{{cite journal | vauthors = Waterman-Storer CM, Karki S, Holzbaur EL | title = The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 5 | pages = 1634–8 | date = February 1995 | pmid = 7878030 | pmc = 42574 | doi = 10.1073/pnas.92.5.1634 }}
5. ^{{cite journal | vauthors = Berrueta L, Tirnauer JS, Schuyler SC, Pellman D, Bierer BE | title = The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain | journal = Current Biology | volume = 9 | issue = 8 | pages = 425–8 | date = April 1999 | pmid = 10226031 | doi = 10.1016/S0960-9822(99)80190-0 }}
6. ^{{cite journal | vauthors = Karki S, Holzbaur EL | title = Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex | journal = The Journal of Biological Chemistry | volume = 270 | issue = 48 | pages = 28806–11 | date = December 1995 | pmid = 7499404 | doi = 10.1074/jbc.270.48.28806 }}
7. ^{{cite journal | vauthors = Vaughan KT, Vallee RB | title = Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued | journal = The Journal of Cell Biology | volume = 131 | issue = 6 Pt 1 | pages = 1507–16 | date = December 1995 | pmid = 8522607 | pmc = 2120689 | doi = 10.1083/jcb.131.6.1507 }}
8. ^{{cite web | title = Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1639| access-date = }}
9. ^{{cite journal | vauthors = 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 | title = The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression | journal = Nature Genetics | volume = 36 | issue = 5 | pages = 462–70 | date = May 2004 | pmid = 15107855 | doi = 10.1038/ng1352 }}
10. ^{{cite journal | vauthors = Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, Wu C, Mobley W, Fuchs E, Yang Y | title = BPAG1n4 is essential for retrograde axonal transport in sensory neurons | journal = The Journal of Cell Biology | volume = 163 | issue = 2 | pages = 223–9 | date = October 2003 | pmid = 14581450 | pmc = 2173519 | doi = 10.1083/jcb.200306075 }}
11. ^{{cite journal | vauthors = Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB | title = Identification of a novel 135-kDa Grb2-binding protein in osteoclasts | journal = The Journal of Biological Chemistry | volume = 271 | issue = 51 | pages = 33141–7 | date = December 1996 | pmid = 8955163 | doi = 10.1074/jbc.271.51.33141 }}
12. ^{{cite journal | vauthors = Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr FA | title = The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes | journal = Current Biology | volume = 12 | issue = 20 | pages = 1792–5 | date = October 2002 | pmid = 12401177 | doi = 10.1016/s0960-9822(02)01221-6 }}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Waterman-Storer CM, Karki S, Holzbaur EL | title = The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 5 | pages = 1634–8 | date = February 1995 | pmid = 7878030 | pmc = 42574 | doi = 10.1073/pnas.92.5.1634 }}
  • {{cite journal | vauthors = Paschal BM, Holzbaur EL, Pfister KK, Clark S, Meyer DI, Vallee RB | title = Characterization of a 50-kDa polypeptide in cytoplasmic dynein preparations reveals a complex with p150GLUED and a novel actin | journal = The Journal of Biological Chemistry | volume = 268 | issue = 20 | pages = 15318–23 | date = July 1993 | pmid = 8325901 | doi = }}
  • {{cite journal | vauthors = Vaughan KT, Vallee RB | title = Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued | journal = The Journal of Cell Biology | volume = 131 | issue = 6 Pt 1 | pages = 1507–16 | date = December 1995 | pmid = 8522607 | pmc = 2120689 | doi = 10.1083/jcb.131.6.1507 }}
  • {{cite journal | vauthors = Holzbaur EL, Tokito MK | title = Localization of the DCTN1 gene encoding p150Glued to human chromosome 2p13 by fluorescence in situ hybridization | journal = Genomics | volume = 31 | issue = 3 | pages = 398–9 | date = February 1996 | pmid = 8838327 | doi = 10.1006/geno.1996.0068 }}
  • {{cite journal | vauthors = Tokito MK, Howland DS, Lee VM, Holzbaur EL | title = Functionally distinct isoforms of dynactin are expressed in human neurons | journal = Molecular Biology of the Cell | volume = 7 | issue = 8 | pages = 1167–80 | date = August 1996 | pmid = 8856662 | pmc = 275970 | doi = 10.1091/mbc.7.8.1167 }}
  • {{cite journal | vauthors = Sahni M, Zhou XM, Bakiri L, Schlessinger J, Baron R, Levy JB | title = Identification of a novel 135-kDa Grb2-binding protein in osteoclasts | journal = The Journal of Biological Chemistry | volume = 271 | issue = 51 | pages = 33141–7 | date = December 1996 | pmid = 8955163 | doi = 10.1074/jbc.271.51.33141 }}
  • {{cite journal | vauthors = Blangy A, Arnaud L, Nigg EA | title = Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 31 | pages = 19418–24 | date = August 1997 | pmid = 9235942 | doi = 10.1074/jbc.272.31.19418 }}
  • {{cite journal | vauthors = Korthaus D, Wedemeyer N, Lengeling A, Ronsiek M, Jockusch H, Schmitt-John T | title = Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases | journal = Genomics | volume = 43 | issue = 2 | pages = 242–4 | date = July 1997 | pmid = 9244444 | doi = 10.1006/geno.1997.4789 }}
  • {{cite journal | vauthors = Waterman-Storer CM, Karki SB, Kuznetsov SA, Tabb JS, Weiss DG, Langford GM, Holzbaur EL | title = The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 22 | pages = 12180–5 | date = October 1997 | pmid = 9342383 | pmc = 23743 | doi = 10.1073/pnas.94.22.12180 }}
  • {{cite journal | vauthors = Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA | title = Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin | journal = Human Molecular Genetics | volume = 6 | issue = 13 | pages = 2205–12 | date = December 1997 | pmid = 9361024 | doi = 10.1093/hmg/6.13.2205 }}
  • {{cite journal | vauthors = Li SH, Gutekunst CA, Hersch SM, Li XJ | title = Interaction of huntingtin-associated protein with dynactin P150Glued | journal = The Journal of Neuroscience | volume = 18 | issue = 4 | pages = 1261–9 | date = February 1998 | pmid = 9454836 | doi = 10.1523/JNEUROSCI.18-04-01261.1998}}
  • {{cite journal | vauthors = Karki S, LaMonte B, Holzbaur EL | title = Characterization of the p22 subunit of dynactin reveals the localization of cytoplasmic dynein and dynactin to the midbody of dividing cells | journal = The Journal of Cell Biology | volume = 142 | issue = 4 | pages = 1023–34 | date = August 1998 | pmid = 9722614 | pmc = 2132867 | doi = 10.1083/jcb.142.4.1023 }}
  • {{cite journal | vauthors = Collin GB, Nishina PM, Marshall JD, Naggert JK | title = Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome | journal = Genomics | volume = 53 | issue = 3 | pages = 359–64 | date = November 1998 | pmid = 9799602 | doi = 10.1006/geno.1998.5542 }}
  • {{cite journal | vauthors = Tokito MK, Holzbaur EL | title = The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B) | journal = Biochimica et Biophysica Acta | volume = 1442 | issue = 2–3 | pages = 432–6 | date = November 1998 | pmid = 9805007 | doi = 10.1016/S0167-4781(98)00195-X }}
  • {{cite journal | vauthors = Bingham JB, Schroer TA | title = Self-regulated polymerization of the actin-related protein Arp1 | journal = Current Biology | volume = 9 | issue = 4 | pages = 223–6 | date = February 1999 | pmid = 10074429 | doi = 10.1016/S0960-9822(99)80095-5 }}
  • {{cite journal | vauthors = Heimann K, Percival JM, Weinberger R, Gunning P, Stow JL | title = Specific isoforms of actin-binding proteins on distinct populations of Golgi-derived vesicles | journal = The Journal of Biological Chemistry | volume = 274 | issue = 16 | pages = 10743–50 | date = April 1999 | pmid = 10196146 | doi = 10.1074/jbc.274.16.10743 }}
  • {{cite journal | vauthors = Eckley DM, Gill SR, Melkonian KA, Bingham JB, Goodson HV, Heuser JE, Schroer TA | title = Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end | journal = The Journal of Cell Biology | volume = 147 | issue = 2 | pages = 307–20 | date = October 1999 | pmid = 10525537 | pmc = 2174220 | doi = 10.1083/jcb.147.2.307 }}
  • {{cite journal | vauthors = Karki S, Tokito MK, Holzbaur EL | title = A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 7 | pages = 4834–9 | date = February 2000 | pmid = 10671518 | doi = 10.1074/jbc.275.7.4834 }}
  • {{cite journal | vauthors = Vancoillie G, Lambert J, Haeghen YV, Westbroek W, Mulder A, Koerten HK, Mommaas AM, Van Oostveldt P, Naeyaert JM | title = Colocalization of dynactin subunits P150Glued and P50 with melanosomes in normal human melanocytes | journal = Pigment Cell Research | volume = 13 | issue = 6 | pages = 449–57 | date = December 2000 | pmid = 11153697 | doi = 10.1034/j.1600-0749.2000.130607.x }}
{{refend}}

External links

  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=perry GeneReviews/NIH/NCBI/UW entry on Perry syndrome]
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