Caveolin-3 regulates myostatin signaling. Mini-review.

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.

[1]  K. Tsuchida,et al.  Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  L. Tang,et al.  Myostatin DNA vaccine increases skeletal muscle mass and endurance in mice , 2007, Muscle & nerve.

[3]  Se-Jin Lee,et al.  Quadrupling Muscle Mass in Mice by Targeting TGF-ß Signaling Pathways , 2007, PloS one.

[4]  S. Park,et al.  Expression of Caveolin-1 reduces cellular responses to TGF-beta1 through down-regulating the expression of TGF-beta type II receptor gene in NIH3T3 fibroblast cells. , 2007, Biochemical and biophysical research communications.

[5]  I. Richard,et al.  AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency , 2007, Gene Therapy.

[6]  R. Parton,et al.  The multiple faces of caveolae , 2007, Nature Reviews Molecular Cell Biology.

[7]  N. Kaminski,et al.  Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis , 2006, The Journal of experimental medicine.

[8]  K. Tsuchida,et al.  Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition. , 2006, The Journal of clinical investigation.

[9]  J. Molkentin,et al.  Age-dependent effect of myostatin blockade on disease severity in a murine model of limb-girdle muscular dystrophy. , 2006, The American journal of pathology.

[10]  J. Hancock,et al.  Biogenesis of caveolae: a structural model for caveolin-induced domain formation , 2006, Journal of Cell Science.

[11]  M. Matzuk,et al.  Regulation of muscle growth by multiple ligands signaling through activin type II receptors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  T. Khurana,et al.  Myostatin propeptide‐mediated amelioration of dystrophic pathophysiology , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  Jeffrey L. Wrana,et al.  Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling , 2005, Nature Reviews Molecular Cell Biology.

[14]  P. Knaus,et al.  Dynamics and interaction of caveolin-1 isoforms with BMP-receptors , 2005, Journal of Cell Science.

[15]  J. Devesa,et al.  Differential Response to Exogenous and Endogenous Myostatin in Myoblasts Suggests that Myostatin Acts as an Autocrine Factor in Vivo , 2004 .

[16]  K. Tsuchida.  Activins, myostatin and related TGF-beta family members as novel therapeutic targets for endocrine, metabolic and immune disorders. , 2004, Current drug targets. Immune, endocrine and metabolic disorders.

[17]  M. Lisanti,et al.  The biology of caveolae: lessons from caveolin knockout mice and implications for human disease. , 2003, Molecular interventions.

[18]  S. Woodman,et al.  Phosphofructokinase muscle-specific isoform requires caveolin-3 expression for plasma membrane recruitment and caveolar targeting: implications for the pathogenesis of caveolin-related muscle diseases. , 2003, The American journal of pathology.

[19]  T. Rando,et al.  A caveolin-3 mutant that causes limb girdle muscular dystrophy type 1C disrupts Src localization and activity and induces apoptosis in skeletal myotubes , 2003, Journal of Cell Science.

[20]  J. Wrana,et al.  Myostatin Signals through a Transforming Growth Factor β-Like Signaling Pathway To Block Adipogenesis , 2003, Molecular and Cellular Biology.

[21]  Chien-Chang Chen,et al.  Defective membrane repair in dysferlin-deficient muscular dystrophy , 2003, Nature.

[22]  T. Brüning,et al.  Homozygous mutations in caveolin‐3 cause a severe form of rippling muscle disease , 2003, Annals of neurology.

[23]  Robert G. Parton,et al.  Caveolae — from ultrastructure to molecular mechanisms , 2003, Nature Reviews Molecular Cell Biology.

[24]  R. Ahima,et al.  Functional improvement of dystrophic muscle by myostatin blockade , 2002, Nature.

[25]  R. Hewick,et al.  The Myostatin Propeptide and the Follistatin-related Gene Are Inhibitory Binding Proteins of Myostatin in Normal Serum* , 2002, The Journal of Biological Chemistry.

[26]  T. Zimmers,et al.  Induction of Cachexia in Mice by Systemically Administered Myostatin , 2002, Science.

[27]  K. Moriyama,et al.  A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle. , 2002, Biochemical and biophysical research communications.

[28]  Michael P. Lisanti,et al.  Emerging Themes in Lipid Rafts and Caveolae , 2001, Cell.

[29]  I. Nonaka,et al.  The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. , 2001, Human molecular genetics.

[30]  Se-Jin Lee,et al.  Regulation of myostatin activity and muscle growth , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Nöthen,et al.  Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease , 2001, Nature Genetics.

[32]  Y. Sunada,et al.  Transgenic mice expressing mutant caveolin-3 show severe myopathy associated with increased nNOS activity. , 2001, Human molecular genetics.

[33]  Quazi Shakey,et al.  Gdf-8 Propeptide Binds to GDF-8 and Antagonizes Biological Activity by Inhibiting GDF-8 Receptor Binding , 2001, Growth factors.

[34]  B. Langley,et al.  Myostatin, a Negative Regulator of Muscle Growth, Functions by Inhibiting Myoblast Proliferation* , 2000, The Journal of Biological Chemistry.

[35]  M. Lisanti,et al.  Caveolin proteins in signaling, oncogenic transformation and muscular dystrophy. , 2000, Journal of cell science.

[36]  M. Lisanti,et al.  Phenotypic Behavior of Caveolin-3 Mutations That Cause Autosomal Dominant Limb Girdle Muscular Dystrophy (LGMD-1C) , 1999, The Journal of Biological Chemistry.

[37]  Pieter J. de Jong,et al.  Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy , 1998, Nature Genetics.

[38]  F. Zara,et al.  Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy , 1998, Nature Genetics.

[39]  Tsuneya Ikezu,et al.  Identification of Peptide and Protein Ligands for the Caveolin-scaffolding Domain , 1997, The Journal of Biological Chemistry.

[40]  F. Vogel,et al.  VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. , 1995, Molecular biology of the cell.

[41]  F. Sotgia,et al.  Caveolin-1 deficiency (-/-) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. , 2006, The American journal of pathology.

[42]  K. Bushby,et al.  Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3. , 2006, Human molecular genetics.

[43]  A. Phillips,et al.  Interleukin-6 regulation of transforming growth factor (TGF)-beta receptor compartmentalization and turnover enhances TGF-beta1 signaling. , 2005, The Journal of biological chemistry.

[44]  P. Tsao,et al.  Transforming growth factor-beta receptors localize to caveolae and regulate endothelial nitric oxide synthase in normal human endothelial cells. , 2005, The Biochemical journal.

[45]  M. D. de Caestecker,et al.  The transforming growth factor-beta superfamily of receptors. , 2004, Cytokine & growth factor reviews.

[46]  M. Bitzer,et al.  Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. , 2001, The Journal of biological chemistry.

[47]  J. Massagué.  TGF-beta signal transduction. , 1998, Annual review of biochemistry.