PXD037452

PXD037452 is an original dataset announced via ProteomeXchange.

Title	Phosphosite mapping on Vimentin under hypotonic stress
Description	Giant Axonal Neuropathy (GAN) is a pediatric neurodegenerative disease caused by loss-of-function mutations in the E3 ubiquitin ligase adaptor gigaxonin, which is encoded by the GAN (KLHL16) gene. Gigaxonin regulates the degradation of multiple intermediate filament (IF) proteins, including neurofilaments, peripherin, GFAP, and vimentin, which aggregate in GAN patient cells. Understanding how IFs and their aggregates are processed under stress can reveal new GAN disease mechanisms and potential targets for therapy. Here we tested the hypothesis that hypotonic stress-induced vimentin proteolysis is impaired in GAN. In this mass spectrometry-based proteomics analysis, phosphorylation at Ser-412, located at the junction between the central “rod” domain and C-terminal “tail” domain on vimentin, was identified to be involved in this stress response. Over-expression studies using either phospho-deficient (S412A) or phospho-mimic (S412D) mutants revealed that Ser-412 is important for filament organization, solubility dynamics, and cleavage of vimentin upon hypotonic stress exposure. Collectively, our work reveals that osmotic stress induces calpain- and proteasome-mediated vimentin degradation and IF network breakdown.
HostingRepository	PRIDE
AnnounceDate	2022-10-27
AnnouncementXML	Submission_2022-10-27_08:36:01.194.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LauraHerring
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-14 14:45:45	ID requested
⏵ 1	2022-10-27 08:36:01	announced

Dataset with its publication pending

submitter keyword: hypotonic stress, giant axonal neuropathy, filaments,phosphorylation

NatashaSnider
contact affiliation	Cell Biology and Physiology, The University of North Carolina at Chapel Hill
contact email	natasha_snider@med.unc.edu
lab head
LauraHerring
contact affiliation	UNC-Chapel Hill
contact email	laura_herring@med.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037452
     1. Label: PRIDE project
     2. Name: Phosphosite mapping on Vimentin under hypotonic stress