PXD049321

PXD049321 is an original dataset announced via ProteomeXchange.

Title	Identification of SEC61B as a novel regulator of calcium flux and platelet hyperactivity in diabetes mellitus
Description	Platelet hyperactivity contributes to increased cardiovascular thrombosis in diabetes. Intracellular and released proteins control platelet activity however there are limited proteomic studies of the diabetic platelet. We isolated platelets from 34 patients without, and 42 patients with type 2 diabetes, matched by age, sex, and coronary artery disease burden. Using high sensitivity unbiased proteomics, we measured over 2,400 intracellular proteins, and detected >70 released proteins only secreted by diabetic platelets indicative of hyperactivation. Importantly, we uniquely identified endoplasmic reticulum (ER) protein SEC61B increased in hyperglycemic human and mouse platelets. SEC61B was increased in megakaryocytes in mouse models of diabetes with evidence of associated ER stress. SEC61 is known to act as a channel for calcium leak, a key aspect in platelet hyperactivation. We demonstrate that cultured cells overexpressing SEC61B had increased cytoplasmic calcium flux and decreased protein synthesis. In accordance, hyperglycemic mouse platelets mobilized more cytoplasmic calcium and had lower protein synthesis compared with normoglycemic platelets. Independent induction of ER stress increased platelet SEC61B expression and P-selectin mobilization. We propose a mechanism whereby ER stress-induced upregulation of platelet SEC61B leads to increased cytoplasmic calcium, potentially contributing to platelet hyperactivity in diabetes.
HostingRepository	PRIDE
AnnounceDate	2025-04-19
AnnouncementXML	Submission_2025-04-18_21:41:36.314.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Larance
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-11 17:01:42	ID requested
⏵ 1	2025-04-18 21:41:36	announced

Dataset with its publication pending

submitter keyword: SEC61B, calcium, ER stress,diabetes, translocon, platelet

Mark Larance
contact affiliation	Charles Perkins Centre, University of Sydney, Australia
contact email	mark.larance@sydney.edu.au
lab head
Mark Larance
contact affiliation	The University of Sydney
contact email	mark.larance@sydney.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049321
     1. Label: PRIDE project
     2. Name: Identification of SEC61B as a novel regulator of calcium flux and platelet hyperactivity in diabetes mellitus