Rap1 plays role in smooth muscle cell vasoconstriction
(HealthDay) -- The Ras-related small GTPase, Rap1, couples to RhoA, and is involved in relocalization of G protein-coupled α2C-adrenoceptors (α2CARs) in smooth muscle cells derived from human dermal arterioles (microVSM), according to a study published online May 23 in the American Journal of Physiology -- Cell Physiology.
Noting that α2C-ARs mobilize to the cell surface and elicit vasoconstriction in response to cellular stress, Selvi C. Jeyaraj, Ph.D., from the Research Institute at Nationwide Children's Hospital in Columbus, Ohio, and colleagues used microVSM to examine the role of Rap1 in α2C-AR receptor localization.
The researchers found that, in human microVSM, increasing intracellular cyclic adenosine monophosphate activated RhoA, increased α2C-AR expression, and increased F-actin via reorganization of the actin cytoskeleton. The α2C-ARs were mobilized to intracellular filamentous structures and to the plasma membrane, from the perinuclear region. In murine wild-type microVSM there were similar results, coupling Rap1-Rho-actin dynamics to receptor relocalization. In Rap1A-null murine microVSM, this signaling was impaired, and it was rescued by delivery of a constitutively-active (CA) Rap1A mutant. Rap1A-CA or Rho-kinase caused translocation of functional α2C-ARs to the cell surface.
"In summary, our results show Rap1 coupling to RhoA activation and reorganization of the actin cytoskeleton, necessary for translocation of microVSM α2C-ARs," the authors write. "The exact mechanism for α2C-AR translocation by actin remains to be determined and is the focus of ongoing work."
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