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Reliable, easy-to-read patient information on common medical conditions — written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.

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DCTN1

Introduction

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

Function

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)[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]

Interactions

Interactions

DCTN1 has been shown to interact with:

References

References

  1. ↑ 1.0 1.1 Holzbaur EL, Hammarback JA, Paschal BM, Kravit NG, Pfister KK, Vallee RB (June 1991). “Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued”. Nature. 351 (6327): 579–83. doi:10.1038/351579a0. PMID 1828535.
  2. ↑ 2.0 2.1 Urnavicius L, Zhang K, Diamant AG, Motz C, Schlager MA, Yu M, Patel NA, Robinson CV, Carter AP (March 2015). “The structure of the dynactin complex and its interaction with dynein”. Science. 347 (6229): 1441–1446. doi:10.1126/science.aaa4080. PMC 4413427. PMID 25814576.
  3. ↑ Cianfrocco MA, DeSantis ME, Leschziner AE, Reck-Peterson SL (2015). “Mechanism and regulation of cytoplasmic dynein”. Annual Review of Cell and Developmental Biology. 31: 83–108. doi:10.1146/annurev-cellbio-100814-125438. PMC 4644480. PMID 26436706.
  4. ↑ Waterman-Storer CM, Karki S, Holzbaur EL (February 1995). “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. PMC 42574. PMID 7878030.
  5. ↑ 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. PMID 10226031.
  6. ↑ 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. PMID 7499404.
  7. ↑ Vaughan KT, Vallee RB (December 1995). “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. PMC 2120689. PMID 8522607.
  8. ↑ “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 (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. PMID 15107855.
  10. ↑ Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, Wu C, Mobley W, Fuchs E, Yang Y (October 2003). “BPAG1n4 is essential for retrograde axonal transport in sensory neurons”. The Journal of Cell Biology. 163 (2): 223–9. doi:10.1083/jcb.200306075. PMC 2173519. PMID 14581450.
  11. ↑ 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. PMID 8955163.
  12. ↑ 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. PMID 12401177.
Further reading

Further reading

External links