title: The importance of the smooth muscle cytoskeleton to preterm labour.
abstract: Multiple mechanisms have been shown to regulate the onset of labour in a co-operative and complex manner. One factor, myometrial stretch and associated increases in wall tension, has been implicated clinically in the initiation of labour and especially the aetiology of preterm labour. Recent work on the mechanisms involved has led to the finding that the intracellular Ca(2+) requirement for activation of the myometrial contractile filaments increases during gestation. The decreased Ca(2+) sensitivity correlates with an increase in the expression of caldesmon, an actin-binding protein and inhibitor of myosin activation, during pregnancy. In late pregnancy, an increase in extracellular signal-regulated kinase-mediated caldesmon phosphorylation occurs, which appears to reverse the inhibitory action of caldesmon during labour. Force generated by the myometrial contractile filaments is communicated across the plasmalemma to the uterine wall through focal adhesions. Phospho-tyrosine screening and mass spectrometry of stretched myometrial samples identified several stretch-activated focal adhesion proteins. This Src-mediated focal adhesion signalling appears to provide a tunable, i.e. regulated, tension sensor and force transmitter in the myometrial cell. In other parallel studies, biophysical measurements of smooth muscle compliance at both the cellular and tissue levels suggest that decreases in cellular compliance due to changing interactions of the actin cytoskeleton with the focal adhesions may also promote increases in uterine wall tension. These results, taken together, suggest that focal adhesion proteins and their interaction with the cytoskeleton may present a new mode of regulation of uterine contractility.
authors.affiliation: * Sargent College, Boston University, 635 Commonwealth Avenue, Boston, MA 02215, USA. kmorgan@bu.edu.
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Morgan
mesh_terms: D000328:Adult; D003599:Cytoskeleton / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D022001:Focal Adhesions / Q000502:physiology; D006801:Humans; D009130:Muscle, Smooth / Q000503:physiopathology*; D009215:Myometrium / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000503:physiopathology*; D011247:Pregnancy; D014590:Uterine Contraction / Q000502:physiology
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases