Calaminus, S. D. J., Auger, J. M., McCarty, O. J. T., Wakelam, M. J. O., Machesky, L. M. and Watson, S. P. (2007) MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability. Journal of Thrombosis and Haemostasis, 5(10), pp. 2136-2145. (doi: 10.1111/j.1538-7836.2007.02696.x) (PMID:17645784)
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Abstract
Background: MyosinIIs are adenosine triphosphate-driven molecular motors that form part of a cell’s contractile machinery. They are activated by phosphorylation of their light chains, by either activation of myosin light chain (MLC) kinase or inhibition of MLC phosphatase via Rho kinase (ROCK). MyosinIIa phosphorylation underlies platelet rounding and stress fiber formation. Objective: To identify the functional significance of myosinIIa in platelet spreading and thrombus formation on collagen using inhibitors of ROCK (Y27632) and myosinII (blebbistatin). Results: Stress fiber formation on collagen is inhibited by both Y27632 and blebbistatin. A substantial proportion of spread platelets generate internal holes or splits on collagen, presumably because of a reduction in contractile strength. Platelet integrity, however, is maintained. In an in vitro model, thrombus embolization on collagen is increased in the presence of Y27632 and blebbistatin at intermediate shear, leading to a reduction in platelet aggregate growth. Moreover, Y27632 causes a marked reduction in thrombus formation in an in vivo laser-injury model. Conclusions: MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the British Heart Foundation,Wellcome Trust, MRC and American Heart Association.S.D.J. Calaminus holds a BHF Studentship; S.P. Watson is aBHF Chair; L.M. Machesky is a MRC Senior Research FellowG117/569; and O.J.T. McCarty is supported by AHA Grant0665512Z. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Machesky, Professor Laura |
| Authors: | Calaminus, S. D. J., Auger, J. M., McCarty, O. J. T., Wakelam, M. J. O., Machesky, L. M., and Watson, S. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Thrombosis and Haemostasis |
| Publisher: | Wiley |
| ISSN: | 1538-7933 |
| ISSN (Online): | 1538-7836 |
| Published Online: | 23 July 2007 |
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