| Abstract | Caveolins, components of the uncoated invaginations of plasma membrane, regulate signal transduction and vesicular trafflicking. Loss of caveolin-3, resulting from dominant negative mutations of caveolin-3 causes autosomal dominant limb-girdle muscular dystrophy (LGMD) 1C and autosomal dominant rippling muscle disease (AD-RMD). Myostatin, a member of the muscle-specific transforming growth factor (TGF)-beta superfamily, negatively regulates skeletal muscle volume. Herein we review caveolin-3 suppressing of activation of type I myostatin receptor, thereby inhibiting subsequent intracellular signaling. In addition, a mouse model of LGMD1C has shown atrophic myopathy with enhanced myostatin signaling. Myostatin inhibition ameliorates muscular phenotype in the model mouse, accompanied by normalized myostatin signaling. Enhanced myostatin signaling by caveolin-3 mutation in human may contribute to the pathogenesis of LGMD1C. Therefore, myostatin inhibition therapy may be a promising treatment for patients with LGMD1C. More recent studies concerning regulation of TGF-beta superfamily signaling by caveolins have provided new insights into the pathogenesis of several human diseases. |
| Authors | Y Ohsawa, T Okada, A Kuga, S Hayashi, T Murakami, K Tsuchida, S Noji, Y Sunada
(Affiliation: Division of Neurology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki-City, Okayama 701-0192, Japan.)
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| Journal | Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases
(Acta Myol)
Vol. 27
Pg. 19-24
(Jul 2008)
ISSN: 1128-2460 Italy |
| PMID | 19108573
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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| Chemical References |
- CAV3 protein, human
- Caveolin 3
- Myostatin
- Smad Proteins
- Transforming Growth Factor beta
|
| Topics |
- Animals
- Caveolin 3
(genetics, metabolism, physiology)
- Disease Models, Animal
- Humans
- Muscle, Skeletal
(metabolism)
- Muscular Dystrophies, Limb-Girdle
(genetics, metabolism, physiopathology, therapy)
- Mutation
- Myostatin
(antagonists & inhibitors, metabolism, physiology)
- Phosphorylation
- Signal Transduction
(physiology)
- Smad Proteins
(metabolism)
- Transcription, Genetic
(physiology)
- Transforming Growth Factor beta
(metabolism)
|
