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DCTN1 mutations were identified in a family with motor-neuron disease before the discovery in Perry syndrome.
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.
DCTN1 p.K56R in patients with PSP.
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%.
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.
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.
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.
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
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.
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.
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.
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.
Dynactin functions as both a dynamic tether and brake during dynein-driven motility.
HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes
Taken together, topographic and functional interactions between dynactin, importin-beta and RanBP2 are involved in nuclear translocation of IGF-1R.
DCTN1 mutations linked with neurogeneration on Guam.
The results of this study DCTN1 mutations may contribute to disparate neurodegenerative diagnoses, including familial motor neuron disease, parkinsonism, and frontotemporal atrophy.
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.
We identified 2 novel mutations of DCTN1 in patients with Perry syndrome
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
that a single mutation in the DCTN1 gene recapitulates symptoms of Perry syndrome patients
our findings demonstrate that p150(Glued) is particularly required to maintain the function and survival of spinal motor neurons during aging
p75NTR intracellular domain as a retrograde degenerative signal and reveal p150(Glued) deacetylation as a unique mechanism regulating axonal transport
a mouse model expressing disease linked-G59S mutant dynactin p150(Glued) develops motor dysfunction >8 months before loss of motor neurons or dopaminergic degeneration is observed.
These findings uncovered the surprising functional relevance of GTP-bound Arl3 and LC8 for the unloading regulation of dynactin-bound cargo from dynein motor.
Functional relationships between PIK3C3, dynactin, and AnkB promote axonal transport of organelles and are required for normal axon length.
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.
These data unveil a previously unrecognized role for the dynein-dynactin motor complex in osteoclast formation and function.
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.
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.
Melanoregulin interacts with the C-terminal domain of Rab-interacting lysosomal protein (RILP) and forms a complex with RILP and p150(Glued) (also known as dynactin subunit 1, DCTN1), a component of the dynein-dynactin motor complex.
It was shown KASH5 possesses hitherto unknown KASH-related sequences that directly interacted with SUN1 and mediated telomere localization. KASH5 interacted with the microtubule-associated dynein- dynactin complex.
Dctn1 plays an important role in mouse spermiogenesis, and mainly affects the formation of the tail of spermatozoa.
Novel mechanism of retrograde apoptosis, in which caspase-8 complexes directly with axonal dynactin p150Glued to reveal a differential vulnerability of subpopulations of olfactory recepetor neurons to undergo apoptosis.
the N-terminal projection domain of tau binds to the C-terminus of the p150 subunit of the dynactin complex
Alpha-E-catenin functions as a dynamic link between the dynactin complex and actin and, thus, integrates the microtubule and actin cytoskeleton during intracellular trafficking.
Arfaptin physically associates with Glued and other dynactin complex components in the nervous system of both flies and mice and colocalizes with Glued at the Golgi in motor neurons.
It uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes.
multiple independent disruptions of Dynactin function cause a relocation of the photoreceptor nucleus toward the brain
dynein-dynactin, abnormal spindle protein (Asp), and KLP10A have roles in Drosophila spindle pole organization
We conclude that Lis1/dynactin act together to regulate multiple, independent functions in mitotic cells, including spindle formation and cell cycle checkpoint release.
Microtubule binding depends on the N-terminal domain of p150[glued].
Mutants in the Lis1/dynactin complex strongly decrease maximum and average spindle velocity, consistent with this motor complex mediating spindle/cortex forces.
Dynein-dynactin plays a role in excluding dendritic Dscam from axons by retrograde transport.
show that this cell polarity regulator interacts with Glued during central synapse formation.
This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin 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 interacts with dynein intermediate chain by its domains directly binding to dynein and binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein (CAP-Gly) domain in its N-terminus. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause distal hereditary motor neuronopathy type VIIB (HMN7B) which is also known as distal spinal and bulbar muscular atrophy (dSBMA).
150 kDa dynein-associated polypeptide
, dynactin 1 (p150, glued homolog, Drosophila)
, dynactin subunit 1
, dynactin 1
, dynactin subunit 1-like
, dynactin 1, retrograde axonal transport
, dynactin P150
, dynactin 1 (p150, glued homolog)