PXD035713

PXD035713 is an original dataset announced via ProteomeXchange.

Title	Stunted Procoagulant Remodelling in Montreal Platelet Syndrome Kindred with p.V1316M mutation
Description	The Montreal Platelet Syndrome Kindred (MPS) with p.V1316M mutation (2B-VWDMPS) has been associated with chronic macrothrombocytopenia, spontaneous platelet clumping, and mucocutaneous and other bleeding which can be largely prevented by von Willebrand factor concentrate infusion. However, supplemental platelet transfusion has been required on occasions, particularly for severe gastro-intestinal bleeds. This raises the question of whether a previously uncharacterized platelet dysfunction contributes to bleeding diathesis in 2B-VWDMPS patients. We studied the 2 members of the MPS kindred with the most severe bleeding phenotype and addressed this question by coupling quantitative platelet shotgun proteomics and validating biochemical assays, with the systematic analysis of platelet procoagulant membrane dynamics (PMD). Previously, we showed that membrane ballooning, a major procoagulant response of the human platelet after exposure to collagen, is driven by the influx of Na+ and Cl-, followed by the entry of osmotically obliged water. Here, we report in 2B-VWDMPS platelets, loss of the transmembrane chloride channel CLIC1, and reduced chloride ion influx after collagen stimulation. This was associated with diminished membrane ballooning and a distinct phenotypic composition of platelets over fibrillar collagen. Also, 2B-VWDMPS platelets showed marked loss of regulatory, cytoskeletal, and contractile proteins that may account for structure disorganization, giant platelet formation and further reduce the haemostatic response.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:01:19.115.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luiz Gustavo de Almeida
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-02 01:43:45	ID requested
1	2023-08-22 09:17:07	announced
⏵ 2	2024-10-22 06:01:19	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Membrane Ballooning, chloride channel CLIC1, 2B-VWD, Cytoskeletal and Contractile proteins, Actin, Procoagulant Membrane Dynamics, Tubulin,Montreal Platelet Syndrome

Antoine Dufour
contact affiliation	Department of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada; The Hotchkiss Brain Institute, University of Calgary, Alberta, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, Alberta, Canada.
contact email	antoine.dufour@ucalgary.ca
lab head
Luiz Gustavo de Almeida
contact affiliation	University of Calgary
contact email	luizgustavo.biotec@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035713
     1. Label: PRIDE project
     2. Name: Stunted Procoagulant Remodelling in Montreal Platelet Syndrome Kindred with p.V1316M mutation