The association of caveolae, actin, and the dystrophin-glycoprotein complex: a role in smooth muscle phenotype and function?
Smooth muscle cells exhibit phenotypic and mechanical plasticity. During maturation, signalling pathways controlling actin dynamics modulate contractile apparatus-associated gene transcription and contractile apparatus remodelling resulting from length change. Differentiated myocytes accumulate abundant caveolae that evolve from the structural association of lipid rafts with caveolin-1, a protein with domains that confer unique functional properties. Caveolae and caveolin-1 modulate and participate in receptor-mediated signalling, and thus contribute to functional diversity of phenotypically similar myocytes. In mature smooth muscle, caveolae are partitioned into discrete linear domains aligned with structural proteins that tether actin to the extracellular matrix. Caveolin-1 binds with beta-dystroglycan, a subunit of the dystrophin glycoprotein complex (DGC), and with filamin, an actin binding protein that organizes cortical actin, to which integrins and focal adhesion complexes are anchored. The DGC is linked to the actin cytoskeleton by a dystrophin subunit and is a receptor for extracellular laminin. Thus, caveolae and caveolin-associated signalling proteins and receptors are linked via structural proteins to a dynamic filamentous actin network. Despite development of transgenic models to investigate caveolins and membrane-associated actin-linking proteins in skeletal and cardiac muscle function, only superficial understanding of this association in smooth muscle phenotype and function has emerged.
Halayko
Andrew J
AJ
Department of Physiology, University of Manitoba, Winnipeg, Canada. ahalayk@cc.umanitoba.ca
Stelmack
Gerald L
GL
D000199:Actins / Q000502:physiology*; D000818:Animals; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1 / Q000378:metabolism; D049109:Cell Proliferation; D003285:Contractile Proteins / Q000378:metabolism; D003599:Cytoskeleton; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D010641:Phenotype
D000199:Actins; D051242:Caveolin 1; D003285:Contractile Proteins; D016189:Dystrophin; D064448:Filamins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D049030:Dystroglycans