Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate.

Details

Serval ID
serval:BIB_6FB404833925
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate.
Journal
Blood
Author(s)
Mailer R.K., Allende M., Heestermans M., Schweizer M., Deppermann C., Frye M., Pula G., Odeberg J., Gelderblom M., Rose-John S., Sickmann A., Blankenberg S., Huber T.B., Kubisch C., Maas C., Gambaryan S., Firsov D., Stavrou E.X., Butler L.M., Renné T.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
11/03/2021
Peer-reviewed
Oui
Volume
137
Number
10
Pages
1392-1405
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in platelets and was implicated in thrombosis in vivo. We used bioinformatic analyses of omics data to identify XPR1 as a major phosphate transporter in platelets. XPR1 messenger RNA and protein expression inversely correlated with intracellular polyphosphate content and release. Pharmacological interference with XPR1 activity increased polyphosphate stores, led to enhanced platelet-driven coagulation, and amplified thrombus formation under flow via the polyphosphate/factor XII pathway. Conditional gene deletion of Xpr1 in platelets resulted in polyphosphate accumulation, accelerated arterial thrombosis, and augmented activated platelet-driven pulmonary embolism without increasing bleeding in mice. These data identify platelet XPR1 as an integral regulator of platelet polyphosphate metabolism and reveal a fundamental role for phosphate homeostasis in thrombosis.
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2020 12:58
Last modification date
15/05/2021 6:31
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