PXD014260 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Therapy, Congenital Disorder of Glycosylation, Gmppa, Myopathy,Skeletal muscle, Dystroglycan |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD014260
- Label: PRIDE project
- Name: Gmppa defects result in a treatable syndromic myopathy with α-Dystroglycan hyperglycosylation