Interaction between mitsugumin 29 and TRPC3 participates in regulating Ca2+ transients in skeletal muscle

Abstract

Mitsugumin 29 (MG29) is related to the fatigue and aging processes of skeletal muscle. To examine the roles of MG29 in conjunction with its binding protein, the canonical-type transient receptor potential cation channel 3 (TRPC3), in skeletal muscle, the binding region of MG29 to TRPC3 was studied along with the functional relevance of the binding in mouse primary skeletal myotubes using co-immunoprecipitation assays and Ca2+ imaging experiments. The N-terminus and the I–II loop of MG29 constitute the binding region for TRPC3. The myotubes that expressed the MG29 mutant missing the entire TRPC3-binding region showed a disrupted binding between endogenous MG29 and TRPC3 and a reduction in Ca2+ transients in response to membrane depolarization without affecting ryanodine receptor 1 activity, the resting cytosolic Ca2+ level, and the amount of releasable Ca2+ from the sarcoplasmic reticulum. Among the proteins mediating Ca2+ movements in skeletal muscle, TRPC4 expression was significantly decreased by the MG29 mutant. Therefore, MG29 could be a new factor for regulating Ca2+ transients during skeletal muscle contraction possibly via a correlation with TRPC3 and TRPC4.