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Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule. Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon. Plays a role in metaphase spindle orientation. Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole. Plays a role in primary cilia formation.
Gene References into Functions
DCTN1 mutations were identified in a family with motor-neuron disease before the discovery in Perry syndrome. PMID: 28625595
ASK1- induced phosphorylation of EB1 not only increases its plus end-tracking ability, but also promotes its recruitment of CLIP170 and p150glued to astral microtubules. PMID: 28039481
Results suggested that variants in DCTN1 are not common risk factors for Chinese sporadic amyotrophic lateral sclerosis and that the frequency of variants of unknown significance in the cohort study was 0.39%. PMID: 28792508
This work reveals the structural details of Hook3's interaction with dynein and offers insight into how cargo adaptors form processive dynein-dynactin motor complexes. PMID: 27482052
No DCTN1 variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of inherited peripheral neuropathies. PMID: 26662454
Mutations in the Dynactin 1 (DCTN1) gene have been demonstrated to result in various neurodegenerative diseases, including distal hereditary motor neuropathy type 7B. In the present study, a p.G59S mutation was identified as the underlying cause of Distal hereditary motor neuropathy type 7B in two families, and their detailed clinical features were characterized. PMID: 27573046
Study found that in peripheral blood mononuclear cells the median expression of KIFC3, KIF1B, and KIF5C was much lower than the expression of dynactin subunits DCTN1 and DCTN3, in both sporadic amyotrophic lateral sclerosis and healthy cases PMID: 26954557
Data suggest that cargo concentration at ERES is regulated by p150(glued) to coordinate protein sorting and transport carrier formation with the subsequent long-range transport towards the Golgi complex along microtubules. PMID: 26459637
Study shows p150glued located at the centrosome in a cell cycle-dependent manner where it is abundant during G1/S phase, located in the minus-end of microtubules during G2/M phase and at the minus-end of microtubules in the mitotic phase. PMID: 25774020
We find that LRRK1-mediated phosphorylation of CLIP-170 causes the accumulation of p150(Glued) (also known as DCTN1) a subunit of dynactin, at microtubule plus ends, thereby facilitating the migration of EGFR-containing endosomes. PMID: 25413345
The results describe the mutant dynactin p150Glued mouse model of motor neuron disease and show that genetic background influences phenotype in part through a region of chromosome 17 supporting the presence of genetic modifiers. PMID: 25763819
Dynactin functions as both a dynamic tether and brake during dynein-driven motility. PMID: 25185702
HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes PMID: 25189619
Taken together, topographic and functional interactions between dynactin, importin-beta and RanBP2 are involved in nuclear translocation of IGF-1R. PMID: 24909165
DCTN1 mutations linked with neurogeneration on Guam. PMID: 25558820
The results of this study DCTN1 mutations may contribute to disparate neurodegenerative diagnoses, including familial motor neuron disease, parkinsonism, and frontotemporal atrophy. PMID: 24676999
The data of this study showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene. PMID: 24797316
We identified 2 novel mutations of DCTN1 in patients with Perry syndrome PMID: 24484619
The fact that SLK (LOSK) phosphorylates only a minor isoform 1A of p150(Glued) suggests that transport and microtubule-organizing functions of dynactin are distinctly divided between the two isoforms PMID: 23985322
A DCTN1 point mutation was identified in a large family with progressive supranuclear palsy. PMID: 24343258
Data find that dynactin has multiple functions in neurons, both activating dynein-mediated retrograde axonal transport and enhancing microtubule stability through a novel anti-catastrophe mechanism regulated by tissue-specific isoform expression PMID: 23874158
The results of this study suggested the presence of biological changes caused by some p150 mutants pointing to a potential pathogenetic significance as modifier of the phenotype of the human disease. PMID: 23143281
Aurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued. PMID: 23547029
in addition to its ciliogenic roles, Kif3a recruits p150(Glued) to the subdistal appendages of mother centrioles, critical for centrosomes to function as microtubule-organizing centres. PMID: 23386061
LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. PMID: 22956769
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. PMID: 22777741
The tubule formations were dependent on microtubule interactions, and specifically controlled by Kif16b and dynein 1. PMID: 22357949
mTORC1 activation requires dynein-dependent transport to a position in the cell where it can be activated PMID: 22987636
Data suggest that TRAPPC9 serves to uncouple p150(Glued) from the COPII coat, and to relay the vesicle-dynactin interaction at the target membrane. PMID: 22279557
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. PMID: 22542187
End-binding proteins interact with the CAP-Gly domains of CLIP-170 and p150(glued). PMID: 22119847
Studies indicate that binding of dynactin, LIS1 and NudEL regulate cytoplasmic dynein motor activity. PMID: 22373868
Endosome movement requires an intact dynactin complex to allow p150(Glued) to activate dynein, since p50 over-expression, which disrupts the dynactin complex, inhibits inward movement even though dynein and p150(Glued) remain membrane-bound. PMID: 21915335
DCTN1 mutation in patients with with early stage of Perry syndrome presented with marked autonomic dysfunction including orthostatic hypotension and decreased cardiac uptake with [123]I-metaiodobenzylguanidine scintigram features PMID: 20702129
Par6alpha controls centrosome organization through its association with the dynactin subunit p150(Glued). PMID: 20719959
Data show that polo-like kinase 1 phosphorylation of p150(Glued) might be one major pathway of NEBD regulation. PMID: 20679239
study describes a new family carrying a G71R mutation in the DCTN1 gene; the proband displayed a series of distinctive features not previously described in Perry syndrome PMID: 20437543
demonstrate that the domains harboring mutated CAP-gly domains bind to microtubules but fail to bind to EB1 PMID: 20518521
Disruption of the SNX6-p150(Glued) interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. PMID: 19935774
DCTN1 subunit p150Glued isoforms notable for differential interaction with microtubules. PMID: 19778315
Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued). PMID: 12063394
dysfunction of dynactin-mediated transport can lead to human motor neuron disease PMID: 12627231
neither APC nor p150glued binding domain is necessary for EB1 or EBF3 to induce microtubule bundling PMID: 14514668
role in extension and assembly of adherens junctions in photoreceptor development PMID: 15067220
Heterozygous missense mutations of DCTN1 were found in a sporadic case of ALS (T1249I), 1 pt with familial ALS (M571T), two pts with familial ALS, & two unaffected relatives (R785W). Alleleic variants of DCTN1 may be a genomic risk factor for ALS. PMID: 15326253
The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD. PMID: 16240349
The Gly59Ser mutation disrupts folding of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain, resulting in aggregation of p150Glued protein in vitro and in vivo, accompanied by an increase in cell death in a motor neuron cell line. PMID: 16505168
The function of p150(Glued) in membrane trafficking is not associated with plus-end localization. PMID: 16772339
Dynactin p150(Glued) plays an important role in the functional integrity of the keratinocyte microparasol. PMID: 17344930