PXD034094

PXD034094 is an original dataset announced via ProteomeXchange.

Title	Endoplasmic reticulum protein 5 (ERp5) attenuates platelet endoplasmic reticulum stress and secretion in a mouse model
Description	Extracellular protein disulphide isomerases (PDIs) are required for in vivo thrombus formation in mice. Platelets secrete ~10% of their PDIs upon activation, including PDI, endoplasmic reticulum protein 57 (ERp57), ERp72, ERp46 and ERp5, which promote platelet aggregation. However the role of intracellular PDIs in platelet function is unknown. In the current study, we aimed to characterize the role of ERp5 (gene Pdia6) using platelet conditional knockout mice (Pf4Cre+/ERp5fl/fl). Pf4Cre+/ERp5fl/fl mice developed mild macrothrombocytopenia. Platelets deficient in ERp5 showed a marked increase in constitutive ER stress as indicated by a 2-fold upregulation of ER proteins including PDI, ERp57, ERp72, ERp46, GRP78, calreticulin and the phosphorylation of IRE-1 and eIF2a. The activation of platelet ER stress pathways in Pf4Cre+/ERp5fl/fl mice was associated with increased protein secretion, Ca2+ mobilization and thrombus formation in a carotid injury model. Our results support that ERp5 acts as negative regulator of ER stress response in platelets, and highlight the differential action of intracellular versus extracellular ERp5. The results also indicate a previously unanticipated role of platelet ER stress in platelet secretion. This may have important implications for therapeutic applications of ER stress inhibitors in thrombosis.
HostingRepository	PRIDE
AnnounceDate	2022-12-13
AnnouncementXML	Submission_2022-12-13_00:58:11.036.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MarkLarance
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-25 03:09:05	ID requested
⏵ 1	2022-12-13 00:58:11	announced

Dataset with its publication pending

submitter keyword: platelets,ERP5, mouse

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

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PRIDE project URI

• PRIDE
  1. PXD034094
     1. Label: PRIDE project
     2. Name: Endoplasmic reticulum protein 5 (ERp5) attenuates platelet endoplasmic reticulum stress and secretion in a mouse model