MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability

Simon D J Calaminus, J. M. Auger, Owen McCarty, M. J O Wakelam, L. M. Machesky, S. P. Watson

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2136-2145
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

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Thrombosis
Collagen
Blood Platelets
Maintenance
Stress Fibers
Myosin-Light-Chain Phosphatase
Phosphorylation
Myosin-Light-Chain Kinase
rho-Associated Kinases
Lasers
Adenosine Triphosphate
Light
Y 27632
Wounds and Injuries
Growth
blebbistatin

Keywords

  • Arterial thrombosis
  • Cell signaling
  • MyosinII
  • Platelet morphology
  • Rho kinase
  • RhoA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability. / Calaminus, Simon D J; Auger, J. M.; McCarty, Owen; Wakelam, M. J O; Machesky, L. M.; Watson, S. P.

In: Journal of Thrombosis and Haemostasis, Vol. 5, No. 10, 10.2007, p. 2136-2145.

Research output: Contribution to journalArticle

Calaminus, Simon D J ; Auger, J. M. ; McCarty, Owen ; Wakelam, M. J O ; Machesky, L. M. ; Watson, S. P. / MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability. In: Journal of Thrombosis and Haemostasis. 2007 ; Vol. 5, No. 10. pp. 2136-2145.
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