We and others have shown in smooth muscle cells that depletion of cholesterol or silencing of caveolin-1 expression disrupts the organization of membrane caveolae and alters functional responses, as measured by contractile agonist-induced intracellular Ca 2+ release and force generation (Gosens et al., 2007b;Prakash et al., 2007). Our new **data** are consistent with these observations and those showing a role for the actin cytoskeleton in modulating Ca 2+ responses in several other cell types (Calaghan et al., 2004;Rosado et al., 2000;Sabala et al., 2002), because induced changes in ultrastructure and the protein profile of caveolae were associated with a reduction both sensitivity to MCh and in maximum peak [Ca 2+ ] i . Trimeric G-proteins are sequestered to caveolae through the interaction of -subunits with caveolin-1, and the signaling machinery required to mobilize Ca 2+ within smooth muscle cells is organized in caveolae (Darby et al., 2000;de Weerd and Leeb-Lundberg, 1997;Gosens et al., 2007b;Kifor et al., 1998;Li et al., 1995). Although PLC1 is concentrated at the cell membrane, it is also present throughout the cell, whereas G q is more-or-less membrane specific, where it stably associates with PLC1 to allow for rapid transmission of intracellular signals via GPCRs such as the M3 muscarinic receptor (Dowal et al., 2006). Recent evidence suggests that caveolin-1 can have a regulatory role, promoting dissociation of G subunits from  subunits to facilitate GPCR signal transduction (Sengupta et al., 2008). Interaction between caveolin-1 and -dystroglycan appears to be necessary for such a functional role, because in human airway smooth muscle cells with stably silenced -dystroglycan, PLC1 and G q were lost from caveolae and accumulated in fractions that are typically devoid of caveolae. As this change mirrored that for PTRF/cavin and caveolin-1, it suggests that interaction of caveolae with structural proteins and the actin cytoskeleton supports sequestration of signaling molecules for Ca 2+ mobilization, and enable a regulator role for caveolin-1.