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The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function

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Holbrook, L.-M., Sasikumar, P., Stanley, R. G., Simmonds, A. D., Bicknell, A. B. and Gibbins, J. M. (2012) The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function. Journal of Thrombosis and Haemostasis, 10 (2). pp. 278-288. ISSN 1538-7933

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To link to this article DOI: 10.1111/j.1538-7836.2011.04593.x

Abstract/Summary

Background: Thiol isomerases are a family of endoplasmic reticulum enzymes which orchestrate redox-based modifications of protein disulphide bonds. Previous studies have identified important roles for the thiol isomerases PDI and ERp5 in the regulation of normal platelet function. Objectives: Recently, we demonstrated the presence of a further five thiol isomerases at the platelet surface. In this report we aim to report the role of one of these enzymes - ERp57 in the regulation of platelet function. Methods/Results: Using enzyme activity function blocking antibodies, we demonstrate a role for ERp57 in platelet aggregation, dense granule secretion, fibrinogen binding, calcium mobilisation and thrombus formation under arterial conditions. In addition to the effects of ERp57 on isolated platelets, we observe the presence of ERp57 in the developing thrombus in vivo. Furthermore the inhibition of ERp57 function was found to reduce laser-injury induced arterial thrombus formation in a murine model of thrombosis. Conclusions: These data suggest that ERp57 is important for normal platelet function and opens up the possibility that the regulation of platelet function by a range of cell surface thiol isomerases may represent a broad paradigm for the regulation of haemostasis and thrombosis.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:26060
Uncontrolled Keywords:ERp5, EPp57, PDI, platelet activation, redox regulation, thiol isomerase, haemostasis, thrombosis
Publisher:Wiley-Blackwell

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