Biphasic myosin II light chain activation during clot retraction

Marion Egot; Alexandre Kauskot; Dominique Lasne; Pascale Gaussem; Christilla Bachelot-Loza

doi:10.1160/TH13-04-0335

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(06): 1215-1222
DOI: 10.1160/TH13-04-0335

Platelets and Blood Cells

Schattauer GmbH

Biphasic myosin II light chain activation during clot retraction

Marion Egot

¹Inserm UMR_S U765, Paris, France

²Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, France

,

Alexandre Kauskot

¹Inserm UMR_S U765, Paris, France

²Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, France

,

Dominique Lasne

¹Inserm UMR_S U765, Paris, France

²Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, France

³AP-HP, Laboratoire d’hématologie, Hôpital Necker, Paris, France

,

Pascale Gaussem

¹Inserm UMR_S U765, Paris, France

²Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, France

⁴AP-HP, Service d’hématologie biologique, Hôpital Européen Georges Pompidou, Paris, France

,

Christilla Bachelot-Loza

¹Inserm UMR_S U765, Paris, France

²Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, France

› Author Affiliations

Abstract

Summary

Clot retraction is an essential step during primary haemostasis, thereby promoting thrombus stability and wound healing. Integrin αIIbβ3 plays a critical role in clot retraction, by inducing acto-myosin interactions that allow platelet cytoskeleton reorganisation. However, the signalling pathways that lead to clot retraction are still misunderstood. In this study, we report the first data on the kinetics of myosin II light chain (MLC) phosphorylation during clot retraction. We found an early phosphorylation peak followed by a second peak. By using specific inhibitors of kinases and small G proteins, we showed that MLC kinase (MLCK), RhoA/ROCK, and Rac-1 were involved in clot retraction and in the early MLC phosphorylation peak. Only Rac-1 and actin polymerisation, controlled by outside-in signalling, were crucial to the second MLC phosphorylation peak.

Keywords

Clot retraction - cytoskeleton - myosin light chain - kinases - signal transduction

Full Text

References

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