PXD004913

PXD004913 is an original dataset announced via ProteomeXchange.

Title	C9ORF72 interaction with cofilin modulates actin dynamics in motoneurons
Description	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.
HostingRepository	PRIDE
AnnounceDate	2016-09-30
AnnouncementXML	Submission_2016-10-17_03:37:28.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-09-11 23:39:49	ID requested
1	2016-09-30 02:48:51	announced
⏵ 2	2016-10-17 03:37:29	announced	Updated publication reference for PubMed record(s): 27723745.

Sivadasan R, Hornburg D, Drepper C, Frank N, Jablonka S, Hansel A, Lojewski X, Sterneckert J, Hermann A, Shaw PJ, Ince PG, Mann M, Meissner F, Sendtner M, C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. Nat Neurosci, 19(12):1610-1618(2016) [pubmed]

curator keyword: Biological

submitter keyword: C9ORF72, ALS, cofilin, FTLD

Felix Meissner
contact affiliation	Experimental Systems Immunology (F. Meissner Group)
contact email	meissner@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/09/PXD004913

PRIDE project URI

• PRIDE
  1. PXD004913
     1. Label: PRIDE project
     2. Name: C9ORF72 interaction with cofilin modulates actin dynamics in motoneurons