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The role of plasma membrane STIM1 and Ca(2+)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, N., Gibbins, J. M. 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
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of 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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