Genomes and Genes
Gene Symbol: p150Glued
Description: dynactin subunit 1
Alias: DAP-150, DP-150, P135, dynactin subunit 1, 150 kDa dynein-associated polypeptide, dynactin 1 (p150, glued homolog, Drosophila)
- Quintyne N, Schroer T. Distinct cell cycle-dependent roles for dynactin and dynein at centrosomes. J Cell Biol. 2002;159:245-54 pubmed..Our results suggest that, in addition to functioning as a microtubule anchor, dynactin contributes to the recruitment of important cell cycle regulators to centrosomes. ..
- Askham J, Vaughan K, Goodson H, Morrison E. Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome. Mol Biol Cell. 2002;13:3627-45 pubmed..We propose that a functional interaction between EB1 and p150(Glued) is required for microtubule minus end anchoring at centrosomes during the assembly and maintenance of a radial microtubule array. ..
- Holleran E, Ligon L, Tokito M, Stankewich M, Morrow J, Holzbaur E. beta III spectrin binds to the Arp1 subunit of dynactin. J Biol Chem. 2001;276:36598-605 pubmed..We hypothesize that the interaction between betaIII spectrin and Arp1 recruits dynein and dynactin to intracellular membranes and provides a direct link between the microtubule motor complex and its membrane-bounded cargo. ..
- Paschal B, Holzbaur E, Pfister K, Clark S, Meyer D, Vallee R. Characterization of a 50-kDa polypeptide in cytoplasmic dynein preparations reveals a complex with p150GLUED and a novel actin. J Biol Chem. 1993;268:15318-23 pubmed..The 150- and 135-kDa polypeptides reacted with an antibody to p150Glued, the mammalian homologue of the Drosophila Glued gene...
- Holleran E, Tokito M, Karki S, Holzbaur E. Centractin (ARP1) associates with spectrin revealing a potential mechanism to link dynactin to intracellular organelles. J Cell Biol. 1996;135:1815-29 pubmed..We suggest a model in which dynactin associates with the Golgi through an interaction between the centractin filament of the dynactin complex and a spectrin-linked cytoskeletal network. ..
- Bingham J, Schroer T. Self-regulated polymerization of the actin-related protein Arp1. Curr Biol. 1999;9:223-6 pubmed..With time, these filaments appeared to anneal to form longer assemblies but never attained the length of conventional actin filaments. ..
- Kim J, Badano J, Sibold S, Esmail M, Hill J, Hoskins B, et al. The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nat Genet. 2004;36:462-70 pubmed
- Laird F, Farah M, Ackerley S, Hoke A, Maragakis N, Rothstein J, et al. Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking. J Neurosci. 2008;28:1997-2005 pubmed publisher..This novel mouse model will be instrumental for not only clarifying disease mechanisms in ALS, but also for testing therapeutic strategies to ameliorate this devastating disease. ..
- Weisbrich A, Honnappa S, Jaussi R, Okhrimenko O, Frey D, Jelesarov I, et al. Structure-function relationship of CAP-Gly domains. Nat Struct Mol Biol. 2007;14:959-67 pubmed..They further establish fundamental roles for the interaction between CAP-Gly proteins and C-terminal EEY/F sequence motifs in regulating complex and dynamic cellular processes. ..
- Fumoto K, Hoogenraad C, Kikuchi A. GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome. EMBO J. 2006;25:5670-82 pubmed..These results imply that GSK-3beta may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization. ..
- Vaughan K, Vallee R. Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. J Cell Biol. 1995;131:1507-16 pubmed..of complex protein samples, the ICs bound specifically to polypeptides of 150 and 135 kD, identified as the p150Glued doublet of the dynactin complex. In reciprocal overlay assays, p150Glued specifically recognized the ICs...
- Tokito M, Howland D, Lee V, Holzbaur E. Functionally distinct isoforms of dynactin are expressed in human neurons. Mol Biol Cell. 1996;7:1167-80 pubmedb>P150Glued is the largest subunit of dynactin, which binds to cytoplasmic dynein and activates vesicle transport along microtubules...
- Holzbaur E, Hammarback J, Paschal B, Kravit N, Pfister K, Vallee R. Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila gene Glued. Nature. 1991;351:579-83 pubmed..As dominant mutations may involve disruption of normal protein-protein interactions, the Glued mutation should provide insight into the mode of action of cytoplasmic dynein in vivo. ..
- Rocha N, Kuijl C, van der Kant R, Janssen L, Houben D, Janssen H, et al. Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. J Cell Biol. 2009;185:1209-25 pubmed publisher..These data explain how the ER and cholesterol control the association of LEs with motor proteins and their positioning in cells. ..
- Goodson H, Skube S, Stalder R, Valetti C, Kreis T, Morrison E, et al. CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms. Cell Motil Cytoskeleton. 2003;55:156-73 pubmed..We find that CLIP-170 mutants alter p150(Glued) localization without affecting EB1, indicating that EB1 can target microtubule plus ends independently of dynactin. ..
- Blangy A, Arnaud L, Nigg E. Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150. J Biol Chem. 1997;272:19418-24 pubmed..Furthermore, they imply that the dynactin complex may functionally interact not only with dynein but also with kinesin-related motors. ..
- Short B, Preisinger C, Schaletzky J, Kopajtich R, Barr F. The Rab6 GTPase regulates recruitment of the dynactin complex to Golgi membranes. Curr Biol. 2002;12:1792-5 pubmed..Other Golgi Rabs do not bind to dynactin and are unable to support its recruitment to membranes. Rab6 therefore functions as a specificity or tethering factor controlling the recruitment of dynactin to membranes. ..
- Waterman Storer C, Karki S, Kuznetsov S, Tabb J, Weiss D, Langford G, et al. The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proc Natl Acad Sci U S A. 1997;94:12180-5 pubmed
- Karki S, LaMonte B, Holzbaur E. Characterization of the p22 subunit of dynactin reveals the localization of cytoplasmic dynein and dynactin to the midbody of dividing cells. J Cell Biol. 1998;142:1023-34 pubmed..We therefore propose that dynein/dynactin complexes may have a novel function during cytokinesis. ..
- Kodani A, Tonthat V, Wu B, Sutterlin C. Par6 alpha interacts with the dynactin subunit p150 Glued and is a critical regulator of centrosomal protein recruitment. Mol Biol Cell. 2010;21:3376-85 pubmed publisher..We propose a model in which Par6? controls centrosome organization through its association with the dynactin subunit p150(Glued). ..
- Hoogenraad C, Akhmanova A, Howell S, Dortland B, De Zeeuw C, Willemsen R, et al. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. EMBO J. 2001;20:4041-54 pubmed..Taken together, these data suggest that mammalian BICD2 plays a role in the dynein- dynactin interaction on the surface of membranous organelles, by associating with these complexes. ..
- Tokito M, Holzbaur E. The genomic structure of DCTN1, a candidate gene for limb-girdle muscular dystrophy (LGMD2B). Biochim Biophys Acta. 1998;1442:432-6 pubmed..Previously we mapped the human gene encoding the p150Glued subunit of dynactin to 2p13, in the vicinity of the locus linked to limb-girdle muscular dystrophy (LGMB2B)...
- Wassmer T, Attar N, Harterink M, van Weering J, Traer C, Oakley J, et al. The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network. Dev Cell. 2009;17:110-22 pubmed publisher..These interactions describe fundamental steps in retromer-mediated transport and establish that the spatial organization of the retromer network is a critical element required for efficient retromer-mediated sorting...
- Kiyomitsu T, Cheeseman I. Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat Cell Biol. 2012;14:311-7 pubmed publisher..We propose that these chromosome- and spindle-pole-derived gradients generate an intrinsic code to control spindle position and orientation. ..
- Dixit R, Levy J, Tokito M, Ligon L, Holzbaur E. Regulation of dynactin through the differential expression of p150Glued isoforms. J Biol Chem. 2008;283:33611-9 pubmed publisherCytoplasmic dynein and dynactin interact to drive microtubule-based transport in the cell. The p150Glued subunit of dynactin binds to dynein, and directly to microtubules...
- 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. ..
- Lloyd T, Machamer J, O Hara K, Kim J, Collins S, Wong M, et al. The p150(Glued) CAP-Gly domain regulates initiation of retrograde transport at synaptic termini. Neuron. 2012;74:344-60 pubmed publisher..Therefore, the p150(Glued) CAP-Gly domain regulates dynein-mediated retrograde transport at synaptic termini, and this function of dynactin is disrupted by a mutation that causes motor neuron disease. ..
- Munch C, Sedlmeier R, Meyer T, Homberg V, Sperfeld A, Kurt A, et al. Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology. 2004;63:724-6 pubmed..The allelic variants of the DCTN1 gene may represent a previously unknown genomic risk factor for ALS. ..
- Ahmed S, Sun S, Siglin A, Polenova T, Williams J. Disease-associated mutations in the p150(Glued) subunit destabilize the CAP-gly domain. Biochemistry. 2010;49:5083-5 pubmed publisher..These data indicate that these disease-associated, point mutations affect the stability of this domain and inhibit their interaction with EB1 but do not inhibit their interaction with microtubules. ..
- Watson P, Stephens D. Microtubule plus-end loading of p150(Glued) is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells. J Cell Sci. 2006;119:2758-67 pubmed..A subset of these structures colocalizes with ER-Golgi transport intermediates. Together, these data show that the function of CLIP-170 and p150(Glued) in membrane trafficking is not associated with their plus-end localization. ..
- Levy J, Sumner C, Caviston J, Tokito M, Ranganathan S, Ligon L, et al. A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation. J Cell Biol. 2006;172:733-45 pubmed..Dynactin is ubiquitously expressed in eukaryotes, but a G59S mutation in the p150Glued subunit of dynactin results in the specific degeneration of motor neurons...
- Matanis T, Akhmanova A, Wulf P, del Nery E, Weide T, Stepanova T, et al. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nat Cell Biol. 2002;4:986-92 pubmed..These data suggest that coordinated action between Rab6a, BICD and the dynein-dynactin complex controls COPI-independent Golgi-ER transport. ..
- Faulkner N, Dujardin D, Tai C, Vaughan K, O Connell C, Wang Y, et al. A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function. Nat Cell Biol. 2000;2:784-91 pubmed..We conclude that LIS1 participates in a subset of dynein functions, and may regulate the division of neuronal progenitor cells in the developing brain. ..
- Waterman Storer C, Karki S, Holzbaur E. The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1). Proc Natl Acad Sci U S A. 1995;92:1634-8 pubmedb>p150Glued was first identified as a polypeptide that copurifies with cytoplasmic dynein, the minus-end-directed microtubule-based motor protein, and has more recently been shown to be present as a member of the oligomeric dynactin ..
- Fokin A, Klementeva T, Nadezhdina E, Burakov A. SLK/LOSK kinase regulates cell motility independently of microtubule organization and Golgi polarization. Cytoskeleton (Hoboken). 2016;73:83-92 pubmed publisher..However, it seems that these events are independent of each other. Thus, SLK/LOSK kinase effectively functions as a switch that links all of the processes underlying cell motility to provide robust directional movement. ..
- Luo Y, Lee I, Jo Y, Namgoong S, Kim N. Depletion of the LINC complex disrupts cytoskeleton dynamics and meiotic resumption in mouse oocytes. Sci Rep. 2016;6:20408 pubmed publisher..Taken together, the results suggest that SUN1 and KASH5 are essential factors in the regulation of meiotic resumption and spindle formation. ..
- KuÅºma Kozakiewicz M, KaÅºmierczak B, Chudy A, Gajewska B, BaraÅ„czyk KuÅºma A. Alteration of Motor Protein Expression Involved in Bidirectional Transport in Peripheral Blood Mononuclear Cells of Patients with Amyotrophic Lateral Sclerosis. Neurodegener Dis. 2016;16:235-44 pubmed publisher..More studies are needed to find out whether the levels of KIF5C and DCTN1 may be useful in ALS diagnosis, and whether KIF1B expression may discriminate ALS from ALS-mimicking disorders. ..
- Mishima T, Ishikawa T, Imamura K, Kondo T, Koshiba Y, Takahashi R, et al. Cytoplasmic aggregates of dynactin in iPSC-derived tyrosine hydroxylase-positive neurons from a patient with Perry syndrome. Parkinsonism Relat Disord. 2016;30:67-72 pubmed publisher..Perry syndrome TH-positive neurons showed dynactin aggregates in cytoplasm. TH-positive neurons from Perry syndrome iPSCs recapitulated an aspect of the disease phenotype of Perry syndrome. ..
- Honda H, Sasagasako N, Shen C, Shijo M, Hamasaki H, Suzuki S, et al. DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy. Parkinsonism Relat Disord. 2018;51:105-110 pubmed publisher..Phosphorylated TARDBP-positive neuronal cytoplasmic inclusions were few. In conjunction with long disease duration and aging, our findings suggest that the F52L DCTN1 mutation may evoke severe tauopathy and moderate ?-synucleinopathy. ..
- Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, et al. Integrated molecular profiling of juvenile myelomonocytic leukemia. Blood. 2018;: pubmed publisher..Crizotinib is a promising candidate drug for the treatment of JMML, particularly in patients with ALK-/ROS1-fusions. ..
- Fuchs E, Short B, Barr F. Assay and properties of rab6 interaction with dynein-dynactin complexes. Methods Enzymol. 2005;403:607-18 pubmed..Standard protocols for yeast two-hybrid analysis, and biochemical assays for the analysis of the interactions between Rab6, Bicaudal-D, and the subunits of the dynein-dynactin complex are outlined. ..
- Uusi Rauva K, Kyttälä A, van der Kant R, Vesa J, Tanhuanpää K, Neefjes J, et al. Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments. Cell Mol Life Sci. 2012;69:2075-89 pubmed publisher..The data presented in this study provide novel insights into the role of CLN3 in late endosomal/lysosomal membrane transport. ..
- 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..However, overexpression of TBCB leads to the decreased localization of p150 to the microtubule network that might result in a functional modulation of this protein complex. ..
- van Lith S, Roodink I, Verhoeff J, MÃ¤kinen P, Lappalainen J, YlÃ¤ Herttuala S, et al. In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued. Oncotarget. 2016;7:71594-71607 pubmed publisher..By using C-C7 as bait in yeast-2-hybrid (Y2H) screens we identified dynactin-1-p150Glued as its binding partner...
- Byers H, Dykstra S, Boissel S. Requirement of dynactin p150(Glued) subunit for the functional integrity of the keratinocyte microparasol. J Invest Dermatol. 2007;127:1736-44 pubmed..The findings provide evidence that dynactin p150(Glued) plays an important role in the functional integrity of the keratinocyte microparasol. ..
- Shimojo M. Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued. J Biol Chem. 2008;283:34880-6 pubmed publisher..Thus, this study suggests that REST/NRSF, dynactin p150(Glued), huntingtin, HAP1, and RILP form a complex involved in the translocation of REST/NRSF into the nucleus and that HAP1 controls REST/NRSF cellular localization in neurons. ..
- Kobayashi T, Miyashita T, Murayama T, Toyoshima Y. Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility. PLoS ONE. 2017;12:e0183672 pubmed publisher..In DCTN1A, the K-rich domain antagonized these inhibitory effects. Therefore, dynactin has two antagonistic domains and promotes or suppresses dynein motility to accomplish correct localization and functions of dynein within a cell. ..
- Munch C, Meyer R, Linke P, Meyer T, Ludolph A, Haas J, et al. The p150 subunit of dynactin (DCTN1) gene in multiple sclerosis. Acta Neurol Scand. 2007;116:231-4 pubmed..The results indicate that the DCTN1 gene is probably not influencing susceptibility to neurodegeneration in MS. ..
- Pushkin A, Abuladze N, Newman D, Tatishchev S, Kurtz I. Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued). Cytogenet Cell Genet. 2001;95:163-8 pubmed..This information should allow the study of potential genomic alterations of DCTN1-SLC4A5 in patients with diseases mapping to this genomic region. ..
- Eckley D, Schroer T. Interactions between the evolutionarily conserved, actin-related protein, Arp11, actin, and Arp1. Mol Biol Cell. 2003;14:2645-54 pubmed..Arp11 significantly decreases the formation of these organized Arp1 assemblies. Finally, this assay was used to confirm the identity of a putative Arp11 homolog in Drosophila melanogaster. ..
- Dumas A, LÃª Bury G, Marie AnaÃ¯s F, Herit F, Mazzolini J, Guilbert T, et al. The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking. J Cell Biol. 2015;211:359-72 pubmed publisher..Thus, we identify Vpr as a modulator of the microtubule-dependent endocytic trafficking in HIV-1-infected macrophages, leading to strong alterations in phagolysosome biogenesis. ..
- Vallee R, McKenney R, Ori McKenney K. Multiple modes of cytoplasmic dynein regulation. Nat Cell Biol. 2012;14:224-30 pubmed publisher..Recent work has distinguished high- and low-load regulatory modes for cytoplasmic dynein, which, combined with a diversity of targeting mechanisms, accounts for a very broad range of functions. ..
- Packham S, Warsito D, Lin Y, Sadi S, Karlsson R, Sehat B, et al. Nuclear translocation of IGF-1R via p150(Glued) and an importin-?/RanBP2-dependent pathway in cancer cells. Oncogene. 2015;34:2227-38 pubmed publisher..Our results provide new understanding of IGF-1R in cancer, which in turn may contribute to development of new therapeutic strategies. ..
- Felicio A, Dinelle K, Agarwal P, Mckenzie J, Heffernan N, Road J, et al. In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers. Mov Disord. 2014;29:1197-201 pubmed publisher..Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene. ..
- Hayashi I, Plevin M, Ikura M. CLIP170 autoinhibition mimics intermolecular interactions with p150Glued or EB1. Nat Struct Mol Biol. 2007;14:980-1 pubmed..Our data thus demonstrate that regulation of microtubule dynamics by plus end-tracking proteins (+TIPs) occurs through direct competition between homologous binding interfaces. ..
- Gustavsson E, Trinh J, Guella I, Szu Tu C, Khinda J, Lin C, et al. DCTN1 p.K56R in progressive supranuclear palsy. Parkinsonism Relat Disord. 2016;28:56-61 pubmed publisher..K56R in patients with PSP. This variant is immediately adjacent to the N-terminal p150(glued) 'CAP-Gly' domain, affects a highly conserved amino acid and alters the protein's affinity to microtubules and its cytoplasmic distribution. ..
- Zaichick S, Bohannon K, Hughes A, Sollars P, Pickard G, Smith G. The herpesvirus VP1/2 protein is an effector of dynein-mediated capsid transport and neuroinvasion. Cell Host Microbe. 2013;13:193-203 pubmed publisher..Thus, VP1/2 tethers PRV capsids to dynein/dynactin to enhance microtubule transport, neuroinvasion, and pathogenesis...
- Schroeder C, Vale R. Assembly and activation of dynein-dynactin by the cargo adaptor protein Hook3. J Cell Biol. 2016;214:309-18 pubmed publisher..Our work reveals the structural details of Hook3's interaction with dynein and offers insight into how cargo adaptors form processive dynein-dynactin motor complexes. ..
- Mishima T, Koga S, Lin W, Kasanuki K, Castanedes Casey M, Wszolek Z, et al. Perry Syndrome: A Distinctive Type of TDP-43 Proteinopathy. J Neuropathol Exp Neurol. 2017;76:676-682 pubmed publisher..parkinsonism with depression, apathy, weight loss, and central hypoventilation caused by mutations in dynactin p150glued (DCTN1). A rare distal hereditary motor neuropathy, HMN7B, also has mutations in DCTN1...
- Chan Y, Fava L, Uldschmid A, Schmitz M, Gerlich D, Nigg E, et al. Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly. J Cell Biol. 2009;185:859-74 pubmed publisher..Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation...
- Zhapparova O, Fokin A, Vorobyeva N, Bryantseva S, Nadezhdina E. Ste20-like protein kinase SLK (LOSK) regulates microtubule organization by targeting dynactin to the centrosome. Mol Biol Cell. 2013;24:3205-14 pubmed publisher..We also show that dynactin phosphorylation is involved in Golgi reorientation in polarized cells. ..
- Stockmann M, Meyer Ohlendorf M, Achberger K, Putz S, Demestre M, Yin H, et al. The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian syndromes. J Neural Transm (Vienna). 2013;120:785-98 pubmed publisherThe dynactin p150glued subunit, encoded by the gene DCTN1 is part of the dynein-dynactin motor protein complex responsible for retrograde axonal transport...
- Sahni M, Zhou X, Bakiri L, Schlessinger J, Baron R, Levy J. Identification of a novel 135-kDa Grb2-binding protein in osteoclasts. J Biol Chem. 1996;271:33141-7 pubmed..The third protein, p135, had a restricted pattern of expression and was present at high levels in authentic osteoclasts and osteoclast-like ..