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Caveolin isoform switch in differentiating C2C12 cells is not prevented by palmitate

Caveolae are membrane invaginations and important for cellular signaling. In skeletal muscle the expression of caveolin‐3 (cav3) is required for normal muscle fiber orientation and function, and caveolin‐1 (cav1) is constitutively expressed. Palmitate (palm) decreases membrane localization of cav3 in cardiomyocytes. Thus, we tested the hypothesis that palm impairs myotube formation in differentiating C2C12 cells. Two time points were tested: 1) After myotube formation: C2C12 myoblasts and myotubes were treated with 0.4 mM palm for 18 hours and 2) during differentiation: C2C12s were treated at 50–60% confluency. Western blot, IP and confocal microscopy determined expression and localization of cav1 and 3. In controls an isoform switch from cav1 in myoblasts to cav3 in myotubes occurred. Palm exposure after tube formation suppressed cav3 expression in confocal images. During differentiation, C2C12s form myotubes in the presence of palm, however the morphology was changed to long and spindly compared to controls. Palm increased the number of myotubes, but considering the changed morphology this suggests inhibition of fusion to larger myotubes. These data suggest that a caveolin isoform switch occurs in the differentiation of C2C12s from cav1 to cav3, and that cav3 expression is important for the correct morphology of myotubes formed.