Loss of muscle-specific Cavin-1 or expression of a Caveolin-3 mutant led to sarcolemmal damage in response to vigorous muscle activity in mouse and zebrafish models.
The caveolin-cavin system provides critical mechanoprotection to the skeletal muscle sarcolemma, preventing damage during vigorous activity.
Dysfunction of caveolae is involved in human muscle disease, although the underlying molecular mechanisms remain unclear. In this paper, we have functionally characterized mouse and zebrafish models of caveolae-associated muscle disease. Using electron tomography, we quantitatively defined the unique three-dimensional membrane architecture of the mature muscle surface. Caveolae occupied around 50% of the sarcolemmal area predominantly assembled into multilobed rosettes. These rosettes were preferentially disassembled in response to increased membrane tension. Caveola-deficient cavin-1(-/-) muscle fibers showed a striking loss of sarcolemmal organization, aberrant T-tubule structures, and increased sensitivity to membrane tension, which was rescued by muscle-specific Cavin-1 reexpression. In vivo imaging of live zebrafish embryos revealed that loss of muscle-specific Cavin-1 or expression of a dystrophy-associated Caveolin-3 mutant both led to sarcolemmal damage but only in response to vigorous muscle activity. Our findings define a conserved and critical role in mechanoprotection for the unique membrane architecture generated by the caveolin-cavin system.
Lo et al. (Mon,) conducted a other in Caveolae-associated muscle disease. Cavin-1 deficiency or Caveolin-3 mutation vs. Wild-type/normal muscle was evaluated on Sarcolemmal organization and response to membrane tension. Loss of muscle-specific Cavin-1 or expression of a Caveolin-3 mutant led to sarcolemmal damage in response to vigorous muscle activity in mouse and zebrafish models.