Increased Rho activation and PKC-mediated smooth muscle contractility in the absence of caveolin-1.

Yulia Shakirova, Johan Bonnevier, Sebastian Albinsson, Mikael Adner, Bengt Rippe, Jonas Broman, Anders Arner, Karl Swärd

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Abstract in Undetermined
Caveolae are omega-shaped membrane invaginations that are abundant in smooth muscle cells. Since many receptors and signaling proteins co-localize with caveolae, these have been proposed to integrate important signaling pathways. The aim of this study was to test whether RhoA/Rho-kinase and protein kinase C (PKC)-mediated Ca2+ sensitization depends on caveolae using caveolin (Cav)-1-deficient (KO) and wild-type (WT) mice. In WT smooth muscle, caveolae were detected and Cav-1, -2 and -3 proteins were expressed. Relative mRNA expression levels were ~15:1:1 for Cav-1, -2, and -3, respectively. Caveolae were absent in KO and reduced levels of Cav-2 and Cav-3 proteins were seen. In intact ileum longitudinal muscle, no differences in the responses to 5-HT or the muscarinic agonist carbachol were found, whereas contraction elicited by endothelin-1 was reduced. Rho activation by GTP{gamma}S was increased in KO compared with WT as shown using a pull-down assay. Following {alpha}-toxin permeabilization, no difference in Ca2+ sensitivity or in Ca2+ sensitization was detected. In KO femoral arteries, phorbol 12,13-dibutyrate (PDBu)-induced and PKC-mediated contraction was increased. This was associated with increased {alpha}1-adrenergic contraction. Following inhibition of PKC, {alpha}1-adrenergic contraction was normalized. PDBu-induced Ca2+ sensitization was not increased in permeabilized femoral arteries. In conclusion, Rho activation, but not Ca2+ sensitization, depends on caveolae in the ileum. Moreover, PKC driven arterial contraction is increased in the absence of caveolin-1. This depends on an intact plasma membrane and is not associated with altered Ca2+ sensitivity.

Ca2+ sensitization; Rho-associated kinase; myosin phosphatase target protein; lipid rafts; CPI-17; G protein-coupled receptor
Originalspråkengelska
Sidor (från-till)C1326-C1335
TidskriftAmerican Journal of Physiology: Cell Physiology
Volym291
Nummer6
DOI
StatusPublished - 2006

Bibliografisk information

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Department of Nephrology (013230024), Department of Clinical Sciences, Malmö (013240000), Cellular Biomechanics (013212075), Vascular and Airway Research (LUR000005), Anaesthesiology and Intensive Care (013230022), Neurophysiology (013212004), Molecular Vascular Physiology (013210031), Clinical and Experimental Allergy Research (013243510)

Ämnesklassifikation (UKÄ)

  • Fysiologi

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