| First Author | Lo HP | Year | 2015 |
| Journal | J Cell Biol | Volume | 210 |
| Issue | 5 | Pages | 833-49 |
| PubMed ID | 26323694 | Mgi Jnum | J:227519 |
| Mgi Id | MGI:5700618 | Doi | 10.1083/jcb.201501046 |
| Citation | Lo HP, et al. (2015) The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. J Cell Biol 210(5):833-49 |
| abstractText | 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. |
