期刊
JOURNAL OF CELL SCIENCE
卷 123, 期 18, 页码 3061-3070出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.066712
关键词
Airway smooth muscle; Dystrophin; Actin; G-protein coupled receptors; Cytoskeleton; Contraction
类别
资金
- Canadian Institute of Health Research (CIHR)
- Canada Research Chair
- Canada Foundation for Innovation
- Manitoba Institute of Child Health (MICH)
- University of Manitoba
- Parker B. Francis Fellowship in Pulmonary Research
- Natural Sciences and Engineering Research Council of Canada (NSERC)
The dystrophin-glycoprotein complex (DGC) links the extracellular matrix and actin cytoskeleton. Caveolae form membrane arrays on smooth muscle cells; we investigated the mechanism for this organization. Caveolin-1 and beta-dystroglycan, the core transmembrane DGC subunit, colocalize in airway smooth muscle. Immunoprecipitation revealed the association of caveolin-1 with beta-dystroglycan. Disruption of actin filaments disordered caveolae arrays, reduced association of beta-dystroglycan and caveolin-1 to lipid rafts, and suppressed the sensitivity and responsiveness of methacholine-induced intracellular Ca2+ release. We generated novel human airway smooth muscle cell lines expressing shRNA to stably silence beta-dystroglycan expression. In these myocytes, caveolae arrays were disorganized, caveolae structural proteins caveolin-1 and PTRF/cavin were displaced, the signaling proteins PLC. 1 and G(alpha q), which are required for receptor-mediated Ca2+ release, were absent from caveolae, and the sensitivity and responsiveness of methacholine-induced intracellular Ca2+ release, was diminished. These data reveal an interaction between caveolin-1 and beta-dystroglycan and demonstrate that this association, in concert with anchorage to the actin cytoskeleton, underpins the spatial organization and functional role of caveolae in receptor-mediated Ca2+ release, which is an essential initiator step in smooth muscle contraction.
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