PXD003719

PXD003719 is an original dataset announced via ProteomeXchange.

Title	The ambiguous Caveolin-3 G55S sequence variant: Muscle biopsy findings and cell biological analysis
Description	Caveolins are structural and functional proteins in plasma membrane invaginations called caveolae. Mutations in Caveolin-3 cause myopathies of variable severity. The pathogenicity of the Caveolin-3 variant G55S is still unclear. Here, we report on three patients suffering from mild to moderate myopathy. In all three patients, but also in two seemingly unaffected family members of patient one the G55S variant was found. Histology revealed moderate chronic myopathic changes and reduced sarcolemmal Caveolin-3 immunoreactivity in all three cases. Immunoblots for Caveolin-3 were abnormal in all cases. By electron microscopy, enlarged caveolae were detected in case one and three and vacuolar myopathy in case two. EM studies of RCMH myoblasts transfected with G55S Caveolin-3 revealed autophagic vacuoles. The alterations in Golgi morphology were in line with pathological Caveolin-3 deposits in this organelle detected by immunofluorescence and indicative for activation of autophagy. Phospho-blotting demonstrated that G55S affects EGFR signaling. Proteomic profiling of transfected RCMH myoblasts demonstrated alterations in levels of physiologically relevant proteins which are indicative for antagonization of G55S Caveolin-3 expression. Some proteomic alterations were enhanced by osmotic/mechanical stress. In conclusion, our results suggest that the G55S Caveolin-3 sequence variant can be compensated by cellular defense mechanisms and that additional stress may lead to vulnerability of G55S Caveolin-3 expressing muscle cells.
HostingRepository	PRIDE
AnnounceDate	2018-07-05
AnnouncementXML	Submission_2018-07-05_06:13:08.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laxmikanth Kollipara
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-02-29 23:38:17	ID requested
⏵ 1	2018-07-05 06:13:09	announced

Brauers E, Roos A, Kollipara L, Zahedi RP, Beckmann A, Mohanadas N, Bauer H, H, ä, usler M, Thoma S, Kress W, Senderek J, Weis J, The Caveolin-3 G56S sequence variant of unknown significance: Muscle biopsy findings and functional cell biological analysis. Proteomics Clin Appl, 11(1-2):(2017) [pubmed]

curator keyword: Biological

submitter keyword: Caveolin-3, LGMD1D, RCMH, proteome profile of muscle cells

Dr. René Zahedi
contact affiliation	Group Leader Protein Dynamics ISAS e.V. Otto-Hahn-Straße 6b 44227 Dortmund, Germany
contact email	rene.zahedi@isas.de
lab head
Laxmikanth Kollipara
contact affiliation	Leibniz – Institut für Analytische Wissenschaften - ISAS - e.V.
contact email	laxmikanth.kollipara@isas.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/2018/07/PXD003719

PRIDE project URI

• PRIDE
  1. PXD003719
     1. Label: PRIDE project
     2. Name: The ambiguous Caveolin-3 G55S sequence variant: Muscle biopsy findings and cell biological analysis