Ambily, A., Kaiser, W. J., Pierro, C., Chamberlain, E. V., Li, Z., Jones, C. I. ORCID: https://orcid.org/0000-0001-7537-1509, Kassouf, N., Gibbins, J. M.
ORCID: https://orcid.org/0000-0002-0372-5352 and Authi, K. S.
(2014)
The role of plasma membrane STIM1 and Ca(2+)entry in platelet aggregation. STIM1 binds to novel proteins in human platelets.
Cellular Signalling, 26 (3).
pp. 502-511.
ISSN 0898-6568
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To link to this item DOI: 10.1016/j.cellsig.2013.11.025
Abstract/Summary
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 |
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Refereed: | Yes |
Divisions: | Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences |
ID Code: | 36658 |
Uncontrolled Keywords: | 1,2-diacyl-sn-glycerol, 1-Oleoyl-2-acetyl-sn-glycerol, Aggregation, Ca(2+) entry, Collagen, DAG, OAG, PM, SOCE, STIM1, TG, TRPC, Thrombospondin-1, plasma membrane, store operated Ca(2+) entry, stromal interaction molecule 1, thapsigargin, transient receptor potential canonical |
Publisher: | Elsevier |
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