The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle

Lo, Harriet P., Nixon, Susan J., Hall, Thomas E., Cowling, Belinda S., Ferguson, Charles, Morgan, Garry P., Schieber, Nicole L., Fernandez-Rojo, Manuel A., Bastiani, Michele, Floetenmeyer, Matthias, Martel, Nick, Laporte, Jocelyn, Pilch, Paul F. and Parton, Robert G. (2015) The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. Journal of Cell Biology, 210 5: 833-849. doi:10.1083/jcb.201501046

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Author Lo, Harriet P.
Nixon, Susan J.
Hall, Thomas E.
Cowling, Belinda S.
Ferguson, Charles
Morgan, Garry P.
Schieber, Nicole L.
Fernandez-Rojo, Manuel A.
Bastiani, Michele
Floetenmeyer, Matthias
Martel, Nick
Laporte, Jocelyn
Pilch, Paul F.
Parton, Robert G.
Title The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle
Journal name Journal of Cell Biology   Check publisher's open access policy
ISSN 0021-9525
Publication date 2015-08
Year available 2015
Sub-type Article (original research)
DOI 10.1083/jcb.201501046
Open Access Status File (Publisher version)
Volume 210
Issue 5
Start page 833
End page 849
Total pages 17
Place of publication Rockefeller University Press
Publisher New York, NY, United States
Collection year 2016
Language eng
Formatted abstract
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.
Keyword Muscular dystrophy
Quantitative analysis
Membrane repair
Wild type
In situ
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
Centre for Microscopy and Microanalysis Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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