PXD014260

PXD014260 is an original dataset announced via ProteomeXchange.

Title	Gmppa defects result in a treatable syndromic myopathy with α-Dystroglycan hyperglycosylation
Description	Mutations in GDP-mannose-pyrophosphorylase-A (Gmppa) are associated with a syndromic disorder with deficits such as muscular hypotonia and weakness, achalasia, alacrima, and mental retardation (AAMR-syndrome). Gmppa is catalytically inactive, while its homolog Gmppb converts GTP and mannose-1-phosphate into GDP-mannose, which is a substrate for protein glycosylation. Suggesting that Gmppa is an allosteric inhibitor of Gmppb, Gmppa and Gmppb interact and disruption of Gmppa in mice increases GDP-mannose tissue levels. KO mice develop a myopathic disorder characterized by hyperglycosylation of the sarcolemma-associated protein α-Dystroglycan (α-Dg), while the overall abundance of α-Dg is reduced. This reduction is also observed in skeletal muscle biopsies of AAMR patients and in myoblasts upon knockdown of Gmppa. The knockdown does not impair myoblast differentiation but compromises myotube maintenance. Dietary mannose depletion prevents α-Dg hyperglycosylation and the deterioration of motor functions in mice. Thus our data suggest that the disorder is at least in part preventable.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:21:05.357.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandro Ori
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-14 08:08:47	ID requested
1	2021-04-15 07:17:20	announced
⏵ 2	2024-10-22 05:21:05	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Therapy, Congenital Disorder of Glycosylation, Gmppa, Myopathy,Skeletal muscle, Dystroglycan

Alessandro Ori
contact affiliation	Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) Beutenbergstrasse 11 07745 Jena, Germany
contact email	alessandro.ori@leibniz-fli.de
lab head
Alessandro Ori
contact affiliation	Leibniz Institute on Aging
contact email	aleori@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014260
     1. Label: PRIDE project
     2. Name: Gmppa defects result in a treatable syndromic myopathy with α-Dystroglycan hyperglycosylation