Microtubule depolymerization facilitates contraction of vascular smooth muscle via increased activation of RhoA/Rho-kinase.
The microtubule network is in a dynamic equilibrium between free and polymerized tubulin, with depolymerization resulting in increased cellular contractility (1-4). Originally, microtubule depolymerization was thought to facilitate contractile responses via the release of an internal, mechanical opposition to contraction. However, recent evidence suggests that depolymerization may also lead to the enhanced activity of various intracellular signaling proteins. The precise signaling pathway by which microtubule depolymerization facilitates vascular smooth muscle contraction is unknown. In non-vascular cells, depolymerization initiates stress fiber formation via increased activity of the small G-protein, RhoA (5-7). The role of this signaling candidate in a calcium-sensitizing contractile pathway is well established. We and others have found it tempting to speculate that RhoA mediates a contractile pathway enhanced by microtubule depolymerization. We further hypothesize the involvement of microtubule depolymerization (via RhoA and Rho-kinase) in the regulation of vascular smooth muscle contraction, with evidence of potential augmentations of this pathway contributing to the increased vasoconstrictor sensitivity seen in various hypertensive animal models.
Chitaley
K
K
Department of Physiology, University of Michigan, Ann Arbor, MI 48019, USA. kanchanc@umich.edu
Webb
R C
RC
D000818:Animals; D002118:Calcium / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008870:Microtubules / Q000502:physiology*; D008955:Models, Cardiovascular; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D002118:Calcium