Dctn1

Summary

Gene Symbol: Dctn1
Description: dynactin 1
Alias: AL022633, DAP-150, DP-150, Glued, p150, p150-glued, p150, dynactin subunit 1, 150 kDa dynein-associated polypeptide, dynactin 1, retrograde axonal transport
Species: mouse
Products:     Dctn1

Top Publications

  1. Moughamian A, Holzbaur E. Dynactin is required for transport initiation from the distal axon. Neuron. 2012;74:331-43 pubmed publisher
    ..Mutations in the CAP-Gly domain disrupt the formation of the motor-cargo complex, highlighting the specific defects in axonal transport that may lead to neurodegeneration. ..
  2. Zhang X, Lei K, Yuan X, Wu X, Zhuang Y, Xu T, et al. SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron. 2009;64:173-87 pubmed publisher
    ..Syne-2 mutants also display severe defects in learning and memory. These results fill an important gap in our understanding of the mechanism of nuclear movement during brain development. ..
  3. Colin E, Zala D, Liot G, Rangone H, Borrell Pages M, Li X, et al. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J. 2008;27:2124-34 pubmed publisher
    ..This also applies to other vesicles suggesting an essential role for huntingtin in the control of vesicular directionality in neurons. ..
  4. Shen Y, Li N, Wu S, Zhou Y, Shan Y, Zhang Q, et al. Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev Cell. 2008;14:342-53 pubmed publisher
    ..Nudel facilitates cell migration by sequestering Cdc42GAP at the leading edge to stabilize active Cdc42 in response to extracellular stimuli. Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP from Nudel. ..
  5. Chang B, Khanna H, Hawes N, Jimeno D, He S, Lillo C, et al. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum Mol Genet. 2006;15:1847-57 pubmed
    ..Our findings suggest a critical function for CEP290 in ciliary transport and provide insights into the mechanism of early-onset photoreceptor degeneration. ..
  6. Chan E, Nasir J, Gutekunst C, Coleman S, Maclean A, Maas A, et al. Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior. Hum Mol Genet. 2002;11:945-59 pubmed
    ..HAP-1 is particularly enriched in the hypothalamus, which is well documented to regulate feeding behavior. Our results demonstrate that HAP-1 plays an essential role in regulating postnatal feeding. ..
  7. Chu T, Tyznik A, Roepke S, Berkley A, Woodward Davis A, Pattacini L, et al. Bystander-activated memory CD8 T cells control early pathogen load in an innate-like, NKG2D-dependent manner. Cell Rep. 2013;3:701-8 pubmed publisher
    ..Together, these data suggest an innate role for memory CD8 T cells in the early immune response before the onset of a de novo generated, antigen-specific CD8 T cell response. ..
  8. Weber J, Jang W, Simin K, Lu W, Yu J, Meisler M. High-resolution genetic, physical, and transcript map of the mnd2 region of mouse chromosome 6. Genomics. 1998;54:107-15 pubmed
    ..The genes described here are positional candidates for the Parkinson disease susceptibility locus PARK3 that was recently mapped to the corresponding region of human chromosome band 2p13.1. ..
  9. Lorenzo D, Badea A, Davis J, Hostettler J, He J, Zhong G, et al. A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport. J Cell Biol. 2014;207:735-52 pubmed publisher
    ..Our results establish new functional relationships between PIK3C3, dynactin, and AnkB that together promote axonal transport of organelles and are required for normal axon length. ..

More Information

Publications40

  1. Jin M, Yamada M, Arai Y, Nagai T, Hirotsune S. Arl3 and LC8 regulate dissociation of dynactin from dynein. Nat Commun. 2014;5:5295 pubmed publisher
    ..Our findings uncovered the surprising functional relevance of GTP-bound Arl3 and LC8 for the unloading regulation of dynactin-bound cargo from dynein motor. ..
  2. Magnani E, Fan J, Gasparini L, Golding M, Williams M, Schiavo G, et al. Interaction of tau protein with the dynactin complex. EMBO J. 2007;26:4546-54 pubmed
    ..We show here for the first time that the N-terminal projection domain of tau binds to the C-terminus of the p150 subunit of the dynactin complex...
  3. Peris L, Thery M, Faure J, Saoudi Y, Lafanechere L, Chilton J, et al. Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. J Cell Biol. 2006;174:839-49 pubmed
    ..In vitro, the head domains of CLIP-170 and of p150 Glued bind more efficiently to tyrosinated microtubules than to detyrosinated polymers...
  4. Lai C, Lin X, Chandran J, Shim H, Yang W, Cai H. The G59S mutation in p150(glued) causes dysfunction of dynactin in mice. J Neurosci. 2007;27:13982-90 pubmed
    The G59S missense mutation at the conserved microtubule-binding domain of p150(glued), a major component of dynein/dynactin complex, has been linked to an autosomal dominant form of motor neuron disease (MND)...
  5. Carson C, Saleh M, Fung F, Nicholson D, Roskams A. Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory receptor neuron apoptosis. J Neurosci. 2005;25:6092-104 pubmed
  6. Gauthier L, Charrin B, Borrell Pages M, Dompierre J, Rangone H, Cordelières F, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell. 2004;118:127-38 pubmed
    ..Huntingtin-mediated transport involves huntingtin-associated protein-1 (HAP1) and the p150(Glued) subunit of dynactin, an essential component of molecular motors...
  7. Kodani A, Salomé Sirerol Piquer M, Seol A, Garcia Verdugo J, Reiter J. Kif3a interacts with Dynactin subunit p150 Glued to organize centriole subdistal appendages. EMBO J. 2013;32:597-607 pubmed publisher
    ..In the absence of Kif3a, the subdistal appendages of centrioles are disorganized and lack p150(Glued) and Ninein...
  8. Li K, Yang L, Zhang C, Niu Y, Li W, Liu J. HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes. J Cell Sci. 2014;127:4574-88 pubmed publisher
    ..Here, we demonstrate that HPS6 directly interacts with the dynactin p150(Glued) subunit of the dynein-dynactin motor complex and acts as cargo adaptor for the retrograde motor to mediate the ..
  9. Nguyen M, Shu T, Sanada K, Lariviere R, Tseng H, Park S, et al. A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons. Nat Cell Biol. 2004;6:595-608 pubmed
    ..Furthermore, variations in levels of NUDEL correlate with disease progression and NF defects in a mouse model of neurodegeneration. Thus, NUDEL contributes to the integrity of CNS neurons by regulating NF assembly. ..
  10. Wiesner D, Sinniger J, Henriques A, Dieterlé S, Müller H, Rasche V, et al. Low dietary protein content alleviates motor symptoms in mice with mutant dynactin/dynein-mediated neurodegeneration. Hum Mol Genet. 2015;24:2228-40 pubmed publisher
    ..Here, we show that a mouse model expressing low levels of disease linked-G59S mutant dynactin p150(Glued) develops motor dysfunction >8 months before loss of motor neurons or dopaminergic degeneration is observed...
  11. Yamada M, Toba S, Takitoh T, Yoshida Y, Mori D, Nakamura T, et al. mNUDC is required for plus-end-directed transport of cytoplasmic dynein and dynactins by kinesin-1. EMBO J. 2010;29:517-31 pubmed publisher
    ..Our findings have uncovered an essential role of mNUDC for anterograde transport of dynein and dynactin by kinesin-1. ..
  12. Ye S, Fowler T, Pavlos N, Ng P, Liang K, Feng Y, et al. LIS1 regulates osteoclast formation and function through its interactions with dynein/dynactin and Plekhm1. PLoS ONE. 2011;6:e27285 pubmed publisher
    ..These results indicate that LIS1 is a previously unrecognized regulator of osteoclast formation, microtubule organization, and lysosomal secretion by virtue of its ability to modulate dynein function and Plekhm1. ..
  13. Ohbayashi N, Maruta Y, Ishida M, Fukuda M. Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p150Glued complex in melanocytes. J Cell Sci. 2012;125:1508-18 pubmed publisher
    ..of Rab-interacting lysosomal protein (RILP) and formed a complex with RILP and p150(Glued) (also known as dynactin subunit 1, DCTN1), a component of the dynein-dynactin motor complex, in cultured cells...
  14. Seldin L, Muroyama A, Lechler T. NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures. elife. 2016;5: pubmed publisher
    ..Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures. ..
  15. Ng P, Cheng T, Zhao H, Ye S, Sm Ang E, Khor E, et al. Disruption of the dynein-dynactin complex unveils motor-specific functions in osteoclast formation and bone resorption. J Bone Miner Res. 2013;28:119-34 pubmed publisher
  16. Jang W, Weber J, Tokito M, Holzbaur E, Meisler M. Mouse p150Glued (dynactin 1) cDNA sequence and evaluation as a candidate for the neuromuscular disease mutation mnd2. Biochem Biophys Res Commun. 1997;231:344-7 pubmed
    ..of 142 kDa and exhibits 95% amino acid sequence identity to the predicted amino acid sequence of human p150Glued (DCTN1)...
  17. Zheng B, Jiang M, Li S, Wu Y, Zhu H, Zhou Z, et al. [Location of Dctn1 in the mouse testis and sperm and its role in spermiogenesis]. Zhonghua Nan Ke Xue. 2011;17:799-804 pubmed
    To investigate the role of dynactin 1 (Dctn1) in the process of mouse spermiogenesis.
  18. Abe T, Tanaka H, Iwanaga T, Odani S, Kuwano R. The presence of the 50-kDa subunit of dynactin complex in the nerve growth cone. Biochem Biophys Res Commun. 1997;233:295-9 pubmed
    ..However, the amount of gmp23-48k in the membrane fraction greatly decreased in adult brain. These results suggest a special role of membrane-associated gmp23-48k/p50 in synapse formation during brain development. ..
  19. Morimoto A, Shibuya H, Zhu X, Kim J, Ishiguro K, Han M, et al. A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis. J Cell Biol. 2012;198:165-72 pubmed publisher
    ..Our study strongly suggests that the meiotic homologue-pairing mechanism mediated by the SUN-KASH NE bridge is highly conserved among eukaryotes. ..
  20. Liu J, Ding J, Kowal A, Nardine T, Allen E, Delcroix J, et al. BPAG1n4 is essential for retrograde axonal transport in sensory neurons. J Cell Biol. 2003;163:223-9 pubmed
    ..We conclude that BPAG1n4 plays an essential role in retrograde axonal transport in sensory neurons. These findings might advance our understanding of pathogenesis of axonal degeneration and neuronal death. ..
  21. Fu M, Holzbaur E. JIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors. J Cell Biol. 2013;202:495-508 pubmed publisher
    ..The direct binding of the dynactin subunit p150(Glued) to JIP1 competitively inhibits KHC activation in vitro and disrupts the transport of APP in neurons...
  22. Liu J, Ding J, Wu C, Bhagavatula P, Cui B, Chu S, et al. Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport. Proc Natl Acad Sci U S A. 2007;104:2223-8 pubmed
    ..Our work lays the foundation for understanding fundamental issues of axonal transport and provides insights into the molecular mechanisms underlying human neurodegenerative disorders. ..
  23. Hashimoto Tane A, Yokosuka T, Sakata Sogawa K, Sakuma M, Ishihara C, Tokunaga M, et al. Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation. Immunity. 2011;34:919-31 pubmed publisher
    ..These results indicate that cSMAC formation by TCR-MC movement depends on dynein and MTs, and the movement regulates T cell activation. ..
  24. Levy J, Holzbaur E. Dynein drives nuclear rotation during forward progression of motile fibroblasts. J Cell Sci. 2008;121:3187-95 pubmed publisher
  25. Kuh G, Stockmann M, Meyer Ohlendorf M, Linta L, Proepper C, Ludolph A, et al. Tubulin-binding cofactor B is a direct interaction partner of the dynactin subunit p150(Glued). Cell Tissue Res. 2012;350:13-26 pubmed publisher
    The dynactin p150(Glued) subunit, encoded by the gene DCTN1, is part of the dynein-dynactin motor protein complex responsible for retrograde axonal transport in motor neurons...
  26. Abe T, Honda T, Takei K, Mikoshiba K, Hoffman Kim D, Jay D, et al. Dynactin is essential for growth cone advance. Biochem Biophys Res Commun. 2008;372:418-22 pubmed publisher
    ..CALI of dynamitin in vitro dissociates another dynactin subunit, p150(Glued), from dynamitin...
  27. Yu J, Lei K, Zhou M, Craft C, Xu G, Xu T, et al. KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development. Hum Mol Genet. 2011;20:1061-73 pubmed publisher
    ..These key retinal developmental signaling results will advance our understanding of the mechanism of nuclear migration in the mammalian retina. ..
  28. Schlager M, Kapitein L, Grigoriev I, Burzynski G, Wulf P, Keijzer N, et al. Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 2010;29:1637-51 pubmed publisher
    ..These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. ..
  29. Lien W, Gelfand V, Vasioukhin V. Alpha-E-catenin binds to dynamitin and regulates dynactin-mediated intracellular traffic. J Cell Biol. 2008;183:989-97 pubmed publisher
  30. Wen Y, Eng C, Schmoranzer J, Cabrera Poch N, Morris E, Chen M, et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol. 2004;6:820-30 pubmed
    ..These results show an evolutionarily conserved pathway for microtubule capture, and suggest that mDia functions as a scaffold protein for EB1 and APC to stabilize microtubules and promote cell migration. ..
  31. Splinter D, Razafsky D, Schlager M, Serra Marques A, Grigoriev I, Demmers J, et al. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol Biol Cell. 2012;23:4226-41 pubmed publisher
    ..Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors...