PXD021876

PXD021876 is an original dataset announced via ProteomeXchange.

Title	Axonal TDP-43 Drives NMJ Disruption through Inhibition of Local Protein Synthesis
Description	Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons of ~95% of ALS patients, but the contribution of axonal TDP-43 to this fatal neurodegenerative disease is unclear. Here, we find TDP-43 accumulation in the axons of intra-muscular nerves from ALS patients, and in motor neurons and neuromuscular junctions(NMJs) of a mouse model with TDP-43 mislocalization. This leads to the formation of G3BP1- and TDP-43-positive RNA-granules in motor neuron axons, and to inhibition of local protein synthesis in axons and NMJs. Specifically, the axonal and synaptic levels of nuclear-encoded mitochondria proteins are reduced. Clearance of axonal TDP-43 restored local translation of the nuclear-encoded mitochondrial proteins and rescued TDP-43-derived axonal and NMJ toxicity. These findings suggest that targeting TDP-43 axonal gain of function may mediata therapeutic effect in ALS.
HostingRepository	PRIDE
AnnounceDate	2021-11-04
AnnouncementXML	Submission_2021-11-04_09:57:21.087.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dominik Priesmann
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-07 07:32:26	ID requested
⏵ 1	2021-11-04 09:57:21	announced

Dataset with its publication pending

submitter keyword: LC-MS/MS, mouse, ALS, TDP-43, NMJ, neurodegeneration

Eran Perlson
contact affiliation	Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
contact email	eranpe@tauex.tau.ac.il
lab head
Dominik Priesmann
contact affiliation	CECAD Research Center University of Cologne 50931 Cologne
contact email	dpriesm3@uni-koeln.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/2021/11/PXD021876

PRIDE project URI

• PRIDE
  1. PXD021876
     1. Label: PRIDE project
     2. Name: Axonal TDP-43 Drives NMJ Disruption through Inhibition of Local Protein Synthesis