PUBLICATION
The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle
- Authors
- Lo, H.P., Nixon, S.J., Hall, T.E., Cowling, B.S., Ferguson, C., Morgan, G.P., Schieber, N.L., Fernandez-Rojo, M.A., Bastiani, M., Floetenmeyer, M., Martel, N., Laporte, J., Pilch, P.F., Parton, R.G.
- ID
- ZDB-PUB-150903-6
- Date
- 2015
- Source
- The Journal of cell biology 210: 833-49 (Journal)
- Registered Authors
- Hall, Thomas, Lo, Harriet, Parton, Robert G.
- Keywords
- none
- MeSH Terms
-
- Animals
- Caveolins/genetics
- Caveolins/metabolism*
- Electron Microscope Tomography
- Mechanotransduction, Cellular*
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Molecular Sequence Data
- Motor Activity/physiology*
- Muscle Fibers, Skeletal/physiology*
- Muscular Dystrophies/genetics
- Muscular Dystrophies/pathology
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism*
- Sarcolemma/genetics
- Sarcolemma/pathology
- Stress, Mechanical*
- Zebrafish
- PubMed
- 26323694 Full text @ J. Cell Biol.
Citation
Lo, H.P., Nixon, S.J., Hall, T.E., Cowling, B.S., Ferguson, C., Morgan, G.P., Schieber, N.L., Fernandez-Rojo, M.A., Bastiani, M., Floetenmeyer, M., Martel, N., Laporte, J., Pilch, P.F., Parton, R.G. (2015) The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. The Journal of cell biology. 210:833-49.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping