Proteomics

Dataset Information

0

C9ORF72 interaction with cofilin modulates actin dynamics in motoneurons

ABSTRACT: Intronic hexanucleotide expansions in C9ORF72 are common in ALS and FTLD, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motoneurons and found that C9ORF72 is present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin is enhanced in C9ORF72 depleted motoneurons, in patient derived lymphoblastoid cells, iPS cell derived motoneurons and post-mortem brain samples from ALS patients. C9ORF72 modulates the activity of the small GTPases Arf6 and Rac1, resulting in enhanced activity of LIMK1/2. This results in reduced axonal actin dynamics in C9ORF72 depleted motoneurons. Dominant negative Arf6 rescues this defect, suggesting that C9ORF72 acts as a modulator of small GTPases in a pathway that regulates axonal actin dynamics.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Amyotrophic Lateral Sclerosis

SUBMITTER: Mario Oroshi  

LAB HEAD: Felix Meissner

PROVIDER: PXD004913 | Pride | 2016-09-30

REPOSITORIES: Pride

Json Xml

Dataset's files

Source:
Action DRS
20121008_Elite1_DaHo_SA_big-IP_carsten_c9orf-contr_1_121029080726.raw Raw
20121008_Elite1_DaHo_SA_big-IP_carsten_c9orf-contr_2.raw Raw
20121008_Elite1_DaHo_SA_big-IP_carsten_c9orf-contr_3_121028213757.raw Raw
20121008_Elite1_DaHo_SA_big-IP_carsten_c9orf-ip_1.raw Raw
20121008_Elite1_DaHo_SA_big-IP_carsten_c9orf-ip_2.raw Raw
Items per page:
1 - 5 of 7
altmetric image

Publications

Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted  ...[more]

Similar Datasets

Transcriptomics Loss of Tdp-43 disrupts the axonal transcriptome of motoneurons accompanied by impaired axonal translation and mitochondria function
2020-07-27 | GSE147607 | GEO
Transcriptomics Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia (Multiplex Analysis of PolyA-linked Sequences)
2013-11-12 | E-GEOD-51684 | biostudies-arrayexpress
Transcriptomics Plastin 3 rescues deficient TrkB/BDNF signaling and protects from dysregulations in Ca2+ homeostasis in SMA mouse models
2023-01-05 | GSE197638 | GEO
Transcriptomics iPSC derived motor neuron cultures from C9ORF72 carriers
2013-11-07 | E-GEOD-52202 | biostudies-arrayexpress
Transcriptomics Neurofilament accumulations in Amyotrophic Lateral Sclerosis patients’ motor neurons impair structural axonal initial segment integrity
2024-07-03 | GSE200474 | GEO
Transcriptomics Impaired local translation of β-actin mRNA in Ighmbp2-deficient motoneurons: implications for spinal muscular atrophy with respiratory distress (SMARD1)
2018-08-21 | GSE111224 | GEO
Transcriptomics Transcriptome Profiling following Neuronal and Glial Expression of ALS-linked SOD1 in Drosophila
2012-07-01 | GSE37148 | GEO
Transcriptomics Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration
2019-01-01 | GSE122069 | GEO
Transcriptomics C9ORF72 GGGGCC expanded repeats produce splicing dysregulation which correlates with disease severity in amyotrophic lateral sclerosis [HuEx-1_0-st]
2015-05-08 | E-GEOD-68607 | biostudies-arrayexpress
Transcriptomics C9orf72 is required for proper macrophage and microglial function in mice
2016-03-24 | GSE77681 | GEO