beta-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release.
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 PLCbeta1 and G(alphaq), 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.
Sharma
Pawan
P
Department of Physiology, University of Manitoba, Winnipeg, MB R3A1R8, Canada.
Ghavami
Saeid
S
Stelmack
Gerald L
GL
McNeill
Karol D
KD
Mutawe
Mark M
MM
Klonisch
Thomas
T
Unruh
Helmut
H
Halayko
Andrew J
AJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D032342:Muscle Cells / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism*; D011485:Protein Binding
D051242:Caveolin 1; D049030:Dystroglycans; D002118:Calcium