The role of plasma membrane STIM1 and Ca2+entry in platelet aggregation. STIM1 binds to novel proteins in human platelets
Ambily, A., Kaiser, W. J., Pierro, C., Chamberlain, E. V., Li, Z., Jones, C. I., Kassouf, Nick 
ORCID: https://orcid.org/0000-0003-0519-1929, Gibbins, J. M. and Authi, K. S.
(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.
ISSN 0898-6568
[Article]
(doi:10.1016/j.cellsig.2013.11.025)
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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.
| Item Type: | Article |
|---|---|
| Additional Information: | Available online 2 December 2013 |
| Research Areas: | A. > School of Science and Technology > Natural Sciences A. > School of Science and Technology > Natural Sciences > Molecular Biology group |
| Item ID: | 19169 |
| Notes on copyright: | 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/ |
| Depositing User: | Nick Kassouf |
| Date Deposited: | 11 Apr 2016 11:19 |
| Last Modified: | 09 Jun 2021 15:45 |
| URI: | https://eprints.mdx.ac.uk/id/eprint/19169 |
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