Genomes and Genes
Summary: A caveolin that is expressed exclusively in MUSCLE CELLS and is sufficient to form CAVEOLAE in SARCOLEMMA. Mutations in caveolin 3 are associated with multiple muscle diseases including DISTAL MYOPATHY and LIMB-GIRDLE MUSCULAR DYSTROPHY.
- Calaghan S, Kozera L, White E. Compartmentalisation of cAMP-dependent signalling by caveolae in the adult cardiac myocyte. J Mol Cell Cardiol. 2008;45:88-92 pubmed publisher..C to disrupt caveolae was confirmed by selective depletion of the buoyant membrane fractions of cholesterol and caveolin 3, the 2 essential components of caveolae...
- Sotgia F, Lee J, Das K, Bedford M, Petrucci T, Macioce P, et al. Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members. J Biol Chem. 2000;275:38048-58 pubmed..We discuss the possible implications of our findings in the context of Duchenne muscular dystrophy. ..
- Tsutsumi Y, Kawaraguchi Y, Horikawa Y, Niesman I, Kidd M, Chin Lee B, et al. Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection. Anesthesiology. 2010;112:1136-45 pubmed publisher..These results show that delayed APC involves translocation of caveolin-3 and glucose transporter-4 to caveolae, resulting in delayed protection in the myocardium. ..
- Wagner E, Lauterbach M, Kohl T, Westphal V, Williams G, Steinbrecher J, et al. Stimulated emission depletion live-cell super-resolution imaging shows proliferative remodeling of T-tubule membrane structures after myocardial infarction. Circ Res. 2012;111:402-14 pubmed publisher..Our data suggest that TT remodeling during HF development involves proliferative membrane changes, early excitation-contraction uncoupling, and network fracturing. ..
- Fujita T, Otsu K, Oshikawa J, Hori H, Kitamura H, Ito T, et al. Caveolin-3 inhibits growth signal in cardiac myoblasts in a Ca2+-dependent manner. J Cell Mol Med. 2006;10:216-24 pubmed..Our findings suggest that caveolin exhibits growth inhibition in a Ca2+-dependent manner, most likely through PKC, in cardiac myoblasts...
- Gervasio O, Whitehead N, Yeung E, Phillips W, Allen D. TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy. J Cell Sci. 2008;121:2246-55 pubmed publisher..Because ROS production is increased in mdx/DMD, these results suggest that a ROS-Src-TRPC1/caveolin-3 pathway contributes to the pathogenesis of mdx/DMD. ..
- Lamb G. Rippling muscle disease may be caused by "silent" action potentials in the tubular system of skeletal muscle fibers. Muscle Nerve. 2005;31:652-8 pubmed..It is suggested that the distinctive contractions in RMD may be due to stretch-induced generation of action potentials within the tubular system. ..
- Volonte D, Peoples A, Galbiati F. Modulation of myoblast fusion by caveolin-3 in dystrophic skeletal muscle cells: implications for Duchenne muscular dystrophy and limb-girdle muscular dystrophy-1C. Mol Biol Cell. 2003;14:4075-88 pubmed..Taken together, these results propose caveolin-3 as a key player in myoblast fusion and suggest that defects of the fusion process may represent additional molecular mechanisms underlying the pathogenesis of DMD and LGMD-1C in humans. ..
- Ziman A, Gómez Viquez N, Bloch R, Lederer W. Excitation-contraction coupling changes during postnatal cardiac development. J Mol Cell Cardiol. 2010;48:379-86 pubmed publisher..Thus we provide the first well-integrated information that links the developing organization of proteins underlying EC coupling (RyR2, DHPR, Cav3 and JP2) to the developing efficacy of EC coupling. ..
- Hezel M, de Groat W, Galbiati F. Caveolin-3 promotes nicotinic acetylcholine receptor clustering and regulates neuromuscular junction activity. Mol Biol Cell. 2010;21:302-10 pubmed publisher..Together, these data identify caveolin-3 as a critical component of the signaling machinery that drives nicotinic acetylcholine receptor clustering and controls neuromuscular junction function. ..
- Biederer C, Ries S, Moser M, Florio M, Israel M, McCormick F, et al. The basic helix-loop-helix transcription factors myogenin and Id2 mediate specific induction of caveolin-3 gene expression during embryonic development. J Biol Chem. 2000;275:26245-51 pubmed
- Hayashi T, Arimura T, Ueda K, Shibata H, Hohda S, Takahashi M, et al. Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2004;313:178-84 pubmed..It was observed that the Thr63Ser mutation reduced the cell surface expression of caveolin-3, albeit the change was mild as compared with the LGMD mutations. These observations suggest that HCM is a clinical spectrum of CAV3 mutations. ..
- Tsutsumi Y, Kawaraguchi Y, Niesman I, Patel H, Roth D. Opioid-induced preconditioning is dependent on caveolin-3 expression. Anesth Analg. 2010;111:1117-21 pubmed publisher..Our results show that opioid-induced preconditioning is dependent on Cav-3 expression and that endogenous protection in Cav-3 overexpressing mice is opioid dependent. ..
- Ostrom R, Bundey R, Insel P. Nitric oxide inhibition of adenylyl cyclase type 6 activity is dependent upon lipid rafts and caveolin signaling complexes. J Biol Chem. 2004;279:19846-53 pubmed..Thus co-localization of multiple signaling components in lipid rafts provides key spatial regulation of AC activity. ..
- Fischer D, Schroers A, Blumcke I, Urbach H, Zerres K, Mortier W, et al. Consequences of a novel caveolin-3 mutation in a large German family. Ann Neurol. 2003;53:233-41 pubmed..Different clinical phenotypes in caveolinopathies may be attributed to so far unidentified modifying factors/genes in the individual genetic background of affected patients. ..
- Gervasio O, Phillips W, Cole L, Allen D. Caveolae respond to cell stretch and contribute to stretch-induced signaling. J Cell Sci. 2011;124:3581-90 pubmed publisher..The stretch-induced unfolding of caveolae, activation of Src and redistribution of caveolin and glycosphingolipids might reflect mechanisms of the cellular adaptation to mechanical stresses. ..
- Park D, Woodman S, Schubert W, Cohen A, Frank P, Chandra M, et al. Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol. 2002;160:2207-17 pubmed..Thus, dual ablation of both Cav-1 and Cav-3 genes in mice leads to a pleiotropic defect in caveolae formation and severe cardiomyopathy. ..
- Schwab W, Galbiati F, Volonte D, Hempel U, Wenzel K, Funk R, et al. Characterisation of caveolins from cartilage: expression of caveolin-1, -2 and -3 in chondrocytes and in alginate cell culture of the rat tibia. Histochem Cell Biol. 1999;112:41-9 pubmed..There is evidence that caveolin-2 and -3 are upregulated during growth and development of articular cartilage, suggesting a role for caveolins in chondrocyte differentiation. ..
- Horikawa Y, Patel H, Tsutsumi Y, Jennings M, Kidd M, Hagiwara Y, et al. Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac protection from hypoxia and ischemia/reperfusion injury. J Mol Cell Cardiol. 2008;44:123-30 pubmed..We conclude that caveolae and caveolin-3 are critical for volatile anesthetic-induced protection of the heart from ischemia/reperfusion injury. ..
- Volonte D, McTiernan C, Drab M, Kasper M, Galbiati F. Caveolin-1 and caveolin-3 form heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis. Am J Physiol Heart Circ Physiol. 2008;294:H392-401 pubmed..Together, these results bring new insight into the functional role of caveolae and suggest that caveolin-1/caveolin-3 heterooligomeric complexes may play a key role in chemotherapy-induced cardiotoxicity in the atria. ..
- Head B, Patel H, Roth D, Lai N, Niesman I, Farquhar M, et al. G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J Biol Chem. 2005;280:31036-44 pubmed
- Gazzerro E, Sotgia F, Bruno C, Lisanti M, Minetti C. Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet. 2010;18:137-45 pubmed publisher..This review will address caveolin-3 biological functions in muscle cells and will describe the muscle and heart disease phenotypes associated with caveolin-3 mutations. ..
- Vassilopoulos S, Oddoux S, Groh S, Cacheux M, Faure J, Brocard J, et al. Caveolin 3 is associated with the calcium release complex and is modified via in vivo triadin modification. Biochemistry. 2010;49:6130-5 pubmed publisher..We also observe an aberrant expression of caveolin 3 in both Trisk 95- and Trisk 51-overexpressing skeletal muscles...
- Feiner E, Chung P, Jasmin J, Zhang J, Whitaker Menezes D, Myers V, et al. Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3. J Card Fail. 2011;17:253-63 pubmed publisher..These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy. ..
- Murakami N, Hayashi Y, Oto Y, Shiraishi M, Itabashi H, Kudo K, et al. Congenital generalized lipodystrophy type 4 with muscular dystrophy: clinical and pathological manifestations in early childhood. Neuromuscul Disord. 2013;23:441-4 pubmed publisher..PTRF immunostaining positivity was absent in the muscle but caveolin-3 was preserved in the sarcolemma at 16 months of age. Secondary deficiency of caveolins may be closely associated with disease progression. ..
- Betz R, Schoser B, Kasper D, Ricker K, Ramirez A, Stein V, et al. Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease. Nat Genet. 2001;28:218-9 pubmed..We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) in all five families analyzed...
- Sotgia F, Woodman S, Bonuccelli G, Capozza F, Minetti C, Scherer P, et al. Phenotypic behavior of caveolin-3 R26Q, a mutant associated with hyperCKemia, distal myopathy, and rippling muscle disease. Am J Physiol Cell Physiol. 2003;285:C1150-60 pubmed..We propose a haploinsufficiency model in which reduced levels of wild-type caveolin-3, although not rendered dysfunctional due to the caveolin-3 R26Q mutant protein, are insufficient for normal muscle cell function. ..
- Mermelstein C, Martins E, Portilho D, Costa M. Association between the muscle-specific proteins desmin and caveolin-3 in muscle cells. Cell Tissue Res. 2007;327:343-51 pubmed..We have thus shown, for the first time, an association between the intermediate filament protein desmin and caveolin-3 in myogenic cells. ..
- Calaghan S, White E. Caveolae modulate excitation-contraction coupling and beta2-adrenergic signalling in adult rat ventricular myocytes. Cardiovasc Res. 2006;69:816-24 pubmed..following MbetaC treatment, and the effect on I(Ca,L) could be mimicked by dialyzing cells with an antibody to caveolin 3. When the G(alphai) pathway was disabled with pertussis toxin (PTX), control cells showed a similar response to ..
- Aboumousa A, Hoogendijk J, Charlton R, Barresi R, Herrmann R, Voit T, et al. Caveolinopathy--new mutations and additional symptoms. Neuromuscul Disord. 2008;18:572-8 pubmed publisher..Presentation with myalgia is common and management of it as well as of myoglobinuria and hypoglycaemia may have a major impact on the patients' quality of life...
- De Souza A, Cohen A, Park D, Woodman S, Tang B, Gutstein D, et al. MR imaging of caveolin gene-specific alterations in right ventricular wall thickness. Magn Reson Imaging. 2005;23:61-8 pubmed..These studies demonstrate the utility of MRI in determining right ventricular wall thickness and underscore the severity of the right ventricular hypertrophy in caveolin null mice. ..
- Vatta M, Ackerman M, Ye B, Makielski J, Ughanze E, Taylor E, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation. 2006;114:2104-12 pubmed..The present study reports the first CAV3 mutations in subjects with LQTS, and we provide functional data demonstrating a gain-of-function increase in late sodium current. ..
- Ballard Croft C, Locklar A, Kristo G, Lasley R. Regional myocardial ischemia-induced activation of MAPKs is associated with subcellular redistribution of caveolin and cholesterol. Am J Physiol Heart Circ Physiol. 2006;291:H658-67 pubmed..These results show the importance of caveolar membrane/lipid rafts in MAPK signaling and suggest that subcellular compartmentation of p44/p42 ERKs and p38 MAPK may play distinct roles in the response to myocardial ischemia-reperfusion. ..
- Fernandez I, Ying Y, Albanesi J, Anderson R. Mechanism of caveolin filament assembly. Proc Natl Acad Sci U S A. 2002;99:11193-8 pubmed..We propose that the heptameric subunit forms in part through lateral interactions between the alpha-helices of the seven Cav(1-101) units. Caveolin-1, therefore, appears to be the structural molecule of the caveolae filamentous coat. ..
- Gómez Ruiz A, De Miguel C, Campion J, Martinez J, Milagro F. Time-dependent regulation of muscle caveolin activation and insulin signalling in response to high-fat diet. FEBS Lett. 2009;583:3259-64 pubmed publisher..Late chronic phase signalling through both proteins was impaired inducing a prediabetic state. Summarizing, caveolins seem to mediate a time-dependent regulation of insulin cascade in response to high-fat diet in muscle. ..
- Catteruccia M, Sanna T, Santorelli F, Tessa A, Di Giacopo R, Sauchelli D, et al. Rippling muscle disease and cardiomyopathy associated with a mutation in the CAV3 gene. Neuromuscul Disord. 2009;19:779-83 pubmed publisher..We suggest that cardiac dysfunction in myopathic patients with CAV3 mutations may be underestimated and recommend a more thorough evaluation for the presence of cardiomyopathy and potentially lethal arrhythmias. ..
- Way M, Parton R. M-caveolin, a muscle-specific caveolin-related protein. FEBS Lett. 1995;376:108-12 pubmed..Epitope-tagged M-caveolin expressed in non-muscle cells was targetted to surface caveolae where it colocalized with endogenous VIP21-caveolin. M-caveolin may play a specialised role in the caveolae of muscle cells. ..
- Ohsawa Y, Okada T, Nishimatsu S, Ishizaki M, Suga T, Fujino M, et al. An inhibitor of transforming growth factor beta type I receptor ameliorates muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy. Lab Invest. 2012;92:1100-14 pubmed publisherSkeletal muscle expressing Pro104Leu mutant caveolin 3 (CAV3(P104L)) in mouse becomes atrophied and serves as a model of autosomal dominant limb-girdle muscular dystrophy 1C...
- Muller J, Piko H, Schoser B, Schlotter Weigel B, Reilich P, Gürster S, et al. Novel splice site mutation in the caveolin-3 gene leading to autosomal recessive limb girdle muscular dystrophy. Neuromuscul Disord. 2006;16:432-6 pubmed..This is the first splicing mutation reported for CAV3. These findings add to the clinical and genetic variability of CAV3 mutations. ..
- Makarewich C, Correll R, Gao H, Zhang H, Yang B, Berretta R, et al. A caveolae-targeted L-type Ca²+ channel antagonist inhibits hypertrophic signaling without reducing cardiac contractility. Circ Res. 2012;110:669-74 pubmed publisher..We provide proof of concept that Ca(2+) influx through LTCCs within caveolae signaling domains can activate "hypertrophic" signaling, and this Ca(2+) influx can be selectively blocked without reducing cardiac contractility. ..
- Quach N, Biressi S, Reichardt L, Keller C, Rando T. Focal adhesion kinase signaling regulates the expression of caveolin 3 and beta1 integrin, genes essential for normal myoblast fusion. Mol Biol Cell. 2009;20:3422-35 pubmed publisher..Intriguingly, the normal increases in the transcript of caveolin 3 as well as an integrin subunit, the beta1D isoform, were suppressed by FAK inhibition...
- Traverso M, Gazzerro E, Assereto S, Sotgia F, Biancheri R, Stringara S, et al. Caveolin-3 T78M and T78K missense mutations lead to different phenotypes in vivo and in vitro. Lab Invest. 2008;88:275-83 pubmed publisher..In conclusion, CAV3 T78M and T78K mutations lead to distinct disorders showing different clinical features and inheritance, and displaying distinct phenotypes in vitro. ..
- Woodman S, Sotgia F, Galbiati F, Minetti C, Lisanti M. Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases. Neurology. 2004;62:538-43 pubmed..This review examines in detail the reported cases of patients with caveolin-3 mutations and their corresponding muscle disease phenotypes...
- Capanni C, Sabatelli P, Mattioli E, Ognibene A, Columbaro M, Lattanzi G, et al. Dysferlin in a hyperCKaemic patient with caveolin 3 mutation and in C2C12 cells after p38 MAP kinase inhibition. Exp Mol Med. 2003;35:538-44 pubmed..studies have reported that dysferlin is implicated in membrane repair mechanism and coimmunoprecipitates with caveolin 3 in human skeletal muscle...
- Hagiwara Y, Nishina Y, Yorifuji H, Kikuchi T. Immunolocalization of caveolin-1 and caveolin-3 in monkey skeletal, cardiac and uterine smooth muscles. Cell Struct Funct. 2002;27:375-82 pubmed..In uterine smooth muscle cells, caveolin-1, but not caveolin-3, was co-immunolocalized with dystrophin on the sarcolemma. ..
- Galbiati F, Engelman J, Volonte D, Zhang X, Minetti C, Li M, et al. Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. J Biol Chem. 2001;276:21425-33 pubmed..These results have clear mechanistic implications for understanding the pathogenesis of LGMD-1C at a molecular level. ..
- Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P, Bado M, et al. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nat Genet. 1998;18:365-8 pubmed..These mutations may interfere with caveolin-3 oligomerization and disrupt caveolae formation at the muscle cell plasma membrane. ..
- Parton R, Way M, Zorzi N, Stang E. Caveolin-3 associates with developing T-tubules during muscle differentiation. J Cell Biol. 1997;136:137-54 pubmed..The results suggest that caveolin-3 transiently associates with T-tubules during development and may be involved in the early development of the T-tubule system in muscle. ..
- Way M, Parton R. M-caveolin, a muscle-specific caveolin-related protein. FEBS Lett. 1996;378:108-12 pubmed..Epitope-tagged M-caveolin expressed in non-muscle cells was targetted to surface caveolae where it colocalized with endogenous VIP21-caveolin. M-caveolin may play a specialised role in the caveolae of muscle cells. ..