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

Shakirova, Yulia LU ; Bonnevier, Johan LU ; Albinsson, Sebastian LU ; Adner, Mikael LU ; Rippe, Bengt LU ; Broman, Jonas LU ; Arner, Anders and Swärd, Karl LU (2006) In American Journal of Physiology: Cell Physiology 291(6). p.1326-1335
Abstract
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,... (More)
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 (Less)
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published
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in
American Journal of Physiology: Cell Physiology
volume
291
issue
6
pages
1326 - 1335
publisher
American Physiological Society
external identifiers
  • wos:000241992000026
  • scopus:33845342531
ISSN
1522-1563
DOI
10.1152/ajpcell.00046.2006
language
English
LU publication?
yes
additional info
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)
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0168aab9-81ea-41b6-961c-ad2ff06b6ed2 (old id 163253)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17102036&dopt=Abstract
date added to LUP
2016-04-01 15:56:53
date last changed
2021-10-06 01:00:45
@article{0168aab9-81ea-41b6-961c-ad2ff06b6ed2,
  abstract     = {Abstract in Undetermined<br/>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.<br/><br/>Ca2+ sensitization; Rho-associated kinase; myosin phosphatase target protein; lipid rafts; CPI-17; G protein-coupled receptor},
  author       = {Shakirova, Yulia and Bonnevier, Johan and Albinsson, Sebastian and Adner, Mikael and Rippe, Bengt and Broman, Jonas and Arner, Anders and Swärd, Karl},
  issn         = {1522-1563},
  language     = {eng},
  number       = {6},
  pages        = {1326--1335},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Cell Physiology},
  title        = {Increased Rho activation and PKC-mediated smooth muscle contractility in the absence of caveolin-1.},
  url          = {http://dx.doi.org/10.1152/ajpcell.00046.2006},
  doi          = {10.1152/ajpcell.00046.2006},
  volume       = {291},
  year         = {2006},
}