PXD016989

PXD016989 is an original dataset announced via ProteomeXchange.

Title	A signaling hub of insulin receptor dystrophin glycoprotein complex and plakoglobin regulates muscle size
Description	Signaling through the insulin receptor governs central physiological functions related to cell growth and metabolism. Here we show by tandem native protein complex purification approach and super-resolution STED microscopy that insulin receptor activity requires association with the fundamental structural module in muscle, the dystrophin glycoprotein complex (DGC), and the desmosomal component plakoglobin (g-catenin). The integrity of this high-molecular-mass assembly renders skeletal muscle susceptibility to insulin because DGC-insulin receptor dissociation by plakoglobin downregulation reduced insulin signaling and caused atrophy. Furthermore, low insulin receptor activity in muscles from transgenic or fasted mice decreased plakoglobin-DGC-insulin receptor content on the plasma membrane, but not when plakoglobin was overexpressed. By masking b-dystroglycan LIR domains, plakoglobin prevents autophagic clearance of plakoglobin-DGC-insulin receptor co-assemblies and maintains their function. Our findings establish DGC as a signaling hub, and provide a possible mechanism for the insulin resistance in Duchenne Muscular Dystrophy, and for the cardiomyopathies seen with plakoglobin mutations.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:50:47.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-07 05:55:41	ID requested
1	2020-03-19 06:55:46	announced
2	2020-03-30 00:16:06	announced	2020-03-30: Updated publication reference for PubMed record(s): 32170063. 2020-03-30: Updated publication reference for DOI(s): 10.1038/s41467-020-14895-9.
⏵ 3	2023-11-14 08:50:48	announced	2023-11-14: Updated project metadata.

Eid Mutlak Y, Aweida D, Volodin A, Ayalon B, Dahan N, Parnis A, Cohen S, A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size. Nat Commun, 11(1):1381(2020) [pubmed]

curator keyword: Biological

submitter keyword: dystrophin,plakoglobin,insulin receptor

Shenhav Cohen
contact affiliation	Department of Biology Technion, Haifa 32000, Israel
contact email	shenhavc@technion.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@tx.technion.ac.il
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/2020/03/PXD016989

PRIDE project URI

• PRIDE
  1. PXD016989
     1. Label: PRIDE project
     2. Name: A signaling hub of insulin receptor dystrophin glycoprotein complex and plakoglobin regulates muscle size