The role of plasma membrane STIM1 and Ca2+entry in platelet aggregation. STIM1 binds to novel proteins in human platelets

Article


Ambily, A., Kaiser, W., Pierro, C., Chamberlain, E., Li, Z., Jones, C., Kassouf, N., Gibbins, J. and Authi, K. 2014. The role of plasma membrane STIM1 and Ca2+entry in platelet aggregation. STIM1 binds to novel proteins in human platelets. Cellular Signalling. 26 (3), pp. 502-511. https://doi.org/10.1016/j.cellsig.2013.11.025
TypeArticle
TitleThe role of plasma membrane STIM1 and Ca2+entry in platelet aggregation. STIM1 binds to novel proteins in human platelets
AuthorsAmbily, A., Kaiser, W., Pierro, C., Chamberlain, E., Li, Z., Jones, C., Kassouf, N., Gibbins, J. and Authi, K.
Abstract

Ca(2+) elevation is essential to platelet activation. STIM1 senses Ca(2+) in the endoplasmic reticulum and activates Orai channels allowing store-operated Ca(2+) entry (SOCE). STIM1 has also been reported to be present in the plasma membrane (PM) with its N-terminal region exposed to the outside medium but its role is not fully understood. We have examined the effects of the antibody GOK/STIM1, which recognises the N-terminal region of STIM1, on SOCE, agonist-stimulated Ca(2+) entry, surface exposure, in vitro thrombus formation and aggregation in human platelets. We also determined novel binding partners of STIM1 using proteomics. The dialysed GOK/STIM1 antibody failed to reduced thapsigargin- and agonist-mediated Ca(2+) entry in Fura2-labelled cells. Using flow cytometry we detect a portion of STIM1 to be surface-exposed. The dialysed GOK/STIM1 antibody reduced thrombus formation by whole blood on collagen-coated capillaries under flow and platelet aggregation induced by collagen. In immunoprecipitation experiments followed by proteomic analysis, STIM1 was found to extract a number of proteins including myosin, DOCK10, thrombospondin-1 and actin. These studies suggest that PM STIM1 may facilitate platelet activation by collagen through novel interactions at the plasma membrane while the essential Ca(2+)-sensing role of STIM1 is served by the protein in the ER.

KeywordsAggregation; Ca2+ entry; Collagen; STIM1; Thrombospondin-1
Research GroupMolecular Biology group
PublisherElsevier
JournalCellular Signalling
ISSN0898-6568
Electronic1873-3913
Publication dates
Online02 Dec 2013
Print01 Mar 2014
Publication process dates
Deposited11 Apr 2016
Submitted25 Oct 2013
Accepted26 Nov 2013
Output statusPublished
Publisher's version
Copyright Statement

Open Access funded by Medical Research Council.
Under a Creative Commons license: Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/3.0/

Digital Object Identifier (DOI)https://doi.org/10.1016/j.cellsig.2013.11.025
Web of Science identifierWOS:000331159700005
LanguageEnglish
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