Regulation by scaffolding proteins of canonical transient receptor potential channels in striated muscle

Recent studies proposed a pivotal role of TRPC channels, in particular TRPC1, in the striated muscle tissue and in the development of calcium mishandling observed in dystrophin-deficient skeletal and cardiac muscle cells (Vandebrouck et al. in J Cell Biol 158: 1089-1096, 2002; Williams and Allen in Am J Physiol Heart Circ Physiol 292: H846-H855, 2007; Stiber et al. in Mol Cell Biol 28: 2637-2647, 2008). In skeletal muscle, TRPCs are proposed to function in a costameric macromolecular complex (Vandebrouck et al. in FASEB J 21: 608-617, 2007; Gervasio et al. in J Cell Sci 121: 2246-2255, 2008) in which scaffolding proteins and dystrophin are central components maintaining normal calcium entry (Stiber et al. in Mol Cell Biol 28: 2637-2647, 2008; Sabourin et al. in J Biol Chem 284: 36248-61, 2009). In this review, we shall summarize the roles played by scaffolding proteins in regulating the calcium entry through TRPC channels of skeletal muscle cells and the implications in muscle physiopathology. Interactions of TRPC1 with caveolin-3, Homer-1 and alpha-syntrophin will be addressed and these complexes will be compared with signalplex in other systems. The mechanosensitive function of scaffolding proteins will be discussed as well as interactions with TRPV2 channels regarding to calcium mishandling in Duchenne dystrophy.