1 RHO protein regulation of contraction in the human uterus

The state of contraction in smooth muscle cells of the human uterus is dependent on the interaction of activated forms of actin and myosin. RHO proteins are small monomeric GTP binding proteins that regulate actin polymerization and myosin phosphorylation in smooth muscle cells. Their action is determined by their level of expression, GTP bound state, intracellular localization and phosphorylated status. Agonist activated RHO proteins bind to effector kinases such as Rho Kinase (ROCK) and diaphanous proteins (DIAPH) to regulate smooth muscle contraction by two mechanisms: ROCK activates smooth muscle myosin (MYL) either by direct phosphorylation at Ser19/Thr18, or thorough inhibition of myosin phosphatase which is a trimeric protein regulated by ROCK and by other protein kinases. Actin polymerizing proteins such as DIAPH1 increase filamentous actin assembly to enhance acto-myosin cross bridge formation and contraction. This review explores recent advances in RHO protein signaling in human myometrium and proposes areas of further research to investigate the involvement of these proteins in the regulation of uterine contractility in pregnancy and labour