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RhoA localization with caveolin-1 regulates vascular contractions to serotonin
Journal article   Open access   Peer reviewed

RhoA localization with caveolin-1 regulates vascular contractions to serotonin

Daniel W Nuno, Sarah K England and Kathryn G Lamping
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.303(9), pp.R959-R967
11/01/2012
DOI: 10.1152/ajpregu.00667.2011
PMCID: PMC3517699
PMID: 22955057
url
https://doi.org/10.1152/ajpregu.00667.2011View
Published (Version of record) Open Access

Abstract

Vascular smooth muscle contraction occurs following an initial response to an increase in intracellular calcium concentration and a sustained response following increases in the sensitivity of contractile proteins to calcium (calcium sensitization). This latter process is regulated by the rhoA/rho kinase pathway and activated by serotonin. In multiple cell types, signaling molecules compartmentalize within caveolae to regulate their activation. We hypothesized that serotonin differentially compartmentalizes rhoA within caveolar versus noncaveolar lipid rafts to regulate sustained vascular contractions. To test this hypothesis, we measured aortic contractions in response to serotonin in wild-type (WT) and cav-1-deficient mice (cav-1 KO). RhoA-dependent contractions in response to serotonin were markedly augmented in arteries from cav-1 KO mice despite a modest reduction in rhoA expression compared with WT. We found that under basal conditions, rhoA in WT arteries was primarily localized within high-density sucrose gradient fractions but temporally shifted to low-density fractions in response to serotonin. In contrast, rhoA in cav-1 KO arteries was primarily in low-density fractions and shifted to high-density fractions in a similar timeframe as that seen in WT mice. We conclude that localization of rhoA to caveolar versus noncaveolar lipid rafts differentially regulates its activation and contractions to rhoA-dependent agonists with greater activation associated with its localization to noncaveolar rafts. Disruption of rhoA localization within caveolae may contribute to increased activation and enhanced vascular contractions in cardiovascular disease.
 lipid rafts Cardiovascular and Renal Integration rho kinase caveolae

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