Article mechanism for human myopathies, possibly involving Cav-3 alteration. ACKNOWLEDGMENT We thank Genethon (Evry, France) for the production of the adenoviruses used in this study. REFERENCES 1. Block, B. A., Imagawa, T., Campbell, K. P., and Franzini-Armstrong, C. (1988) Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticu- lum junction in skeletal muscle. J. Cell Biol. 107, 2587–2600. 2. Marty, I., Robert, M., Villaz, M., Lai, Y., De Jongh, K. S., Catterall, W. A., and Ronjat, M. (1994) Biochemical Evidence for a complex involving Dihydropyridine Receptor and Ryanodine Receptor in Triad Junctions of Skeletal Muscle. Proc. Natl. Acad. Sci. U.S.A. 91, 2270–2274. 3. Marty, I., Thevenon, D., Scotto, C., Groh, S., Sainnier, S., Robert, M., Grunwald, D., and Villaz, M. (2000) Cloning and characteriza- tion of a new isoform of skeletal muscle triadin. J. Biol. Chem. 275, 8206–8212. 4. Smida Rezgui, S., Vassilopoulos, S., Brocard, J., Platel, J. C., Bouron, A., Arnoult, C., Oddoux, S., Garcia, L., De Waard, M., and Marty, I. (2005) Triadin (TRISK 95) over-expression blocks excitation- contraction coupling in rat skeletal myotubes. J. Biol. Chem. 280, 39302–39308. 5. Groh, S., Marty, I., Ottolia, M., Prestipino, G., Chapel, A., Villaz, M., and Ronjat, M. (1999) Functional interaction of the cytoplasmic domain of triadin with the skeletal ryanodine receptor. J. Biol. Chem. 274, 12278–12283. 6. Ohkura, M., Furukawa, K., Fujimori, H., Kuruma, A., Kawano, S., Hiraoka, M., Kuniyasu, A., Nakayama, H., and Ohizumi, Y. (1998) Dual regulation of the skeletal muscle ryanodine receptor by triadin and calsequestrin. Biochemistry 37, 12987–12993. 7. Oddoux, S., Brocard, J., Schweitzer, A., Szentesi, P., Giannesini, B., Brocard, J., Faure, J., Pernet-Gallay, K., Bendahan, D., Lunardi, J., Csernoch, L., and Marty, I. (2009) Triadin deletion induces impaired skeletal muscle function. J. Biol. Chem. 284, 34918–34929. 8. Shen, X., Franzini-Armstrong, C., Lopez, J. R., Jones, L. R., Kobayashi, Y. M., Wang, Y., Kerrick, W. G., Caswell, A. H., Potter, J. D., Miller, T., Allen, P. D., and Perez, C. F. (2007) Triadins modulate intracellular Ca2þ homeostasis but are not essential for excitation-contraction coupling in skeletal muscle. J. Biol. Chem. 282, 7864–7874. 9. Thevenon, D., Smida-Rezgui, S., Chevessier, F., Groh, S., Henry- Berger, J., Romero, N. B., Villaz, V., De Waard, M., and Marty, I. (2003) Human skeletal muscle triadin: Gene organization and cloning of the major isoform, Trisk 51. Biochem. Biophys. Res. Commun. 303, 669–675. 10. Williams, T. M., and Lisanti, M. P. (2004) The caveolin proteins. Genome Biol. 5, 214. 11. Marty, I., Robert, M., Ronjat, M., Bally, I., Arlaud, G., and Villaz, M. (1995) Localization of the N-terminal and C-terminal ends of triadin with respect to the sarcoplasmic reticulum membrane of rabbit skeletal muscle. Biochem. J. 307, 769–774. 12. Enouf, J., Lompre, A. M., Bredoux, R., Bourdeau, N., de La Bastie, D., and Levy-Toledano, S. (1988) Different sensitivity to trypsin of the human platelet plasma and intracellular membrane Ca2þ pumps. J. Biol. Chem. 263, 13922–13929. 13. Vassilopoulos, S., Thevenon, D., Smida Rezgui, S., Brocard, J., Chapel, A., Lacampagne, A., Lunardi, J., DeWaard, M., and Marty, I. (2005) Triadins are not triad-specific proteins: Two new skeletal muscle triadins possibly involved in the architecture of sarcoplasmic reticulum. J. Biol. Chem. 280, 28601–28609. 14. Allamand, V., Donahue, K. M., Straub, V., Davisson, R. L., Davidson, B. L., and Campbell, K. P. (2000) Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in R-sarcoglycan- deficient mice. Gene Ther. 7, 1385–1391. 15. Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelles, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Biochemistry, Vol. 49, No. 29, 2010 6135 Lazaro, L., Martin, J. J., Morava, E., Rossi, A., Van der Kooi, A., Verschuuren, C., and Lunardi, J. (2008) Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores. Hum. Mutat. 29, 670–678. 16. Kobuke, K., Piccolo, F., Garringer, K. W., Moore, S. A., Sweezer, E., Yang, B., and Campbell, K. P. (2008) A common disease-associated missense mutation in R-sarcoglycan fails to cause muscular dystrophy in mice. Hum. Mol. Genet. 17, 1201–1213. 17. Galbiati, F., Engelman, J. A., Volonte, D., Zhang, X. L., Minetti, C., Li, M., Hou, H., Jr., Kneitz, B., Edelmann, W., and Lisanti, M. P. (2001) Caveolin-3 mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and T-tubule abnormalities. J. Biol. Chem. 276, 21425–21433. 18. Couchoux, H., Allard, B., Legrand, C., Jacquemond, V., and Berthier, C. (2007) Loss of caveolin-3 induced by the dystrophy-associated P104L mutation impairs L-type calcium channel function in mouse skeletal muscle cells. J. Physiol. 580, 745–754. 19. Balijepalli, R. C., Foell, J. D., Hall, D. D., Hell, J. W., and Kamp, T. J. (2006) Localization of cardiac L-type Ca2þ channels to a caveolar macromolecular signaling complex is required for β2-adrenergic regulation. Proc. Natl. Acad. Sci. U.S.A. 103, 7500–7505. 20. Head, B. P., Patel, H. H., Roth, D., Lai, N. C., Niesman, I. R., Farquhar, M. G., and Insel, P. A. (2005) G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J. Biol. Chem. 280, 31036–31044. 21. Fujimoto, T., Nakade, S., Miyawaki, A., Mikoshiba, K., and Ogawa, K. (1992) Localization of inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae. J. Cell Biol. 119, 1507–1513. 22. Fujimoto, T. (1993) Calcium pump of the plasma membrane is localized in caveolae. J. Cell Biol. 120, 1147–1157. 23. Isshiki, M., and Anderson, R. G. (2003) Function of caveolae in Ca2þ entry and Ca2þ-dependent signal transduction. Traffic 4, 717–723. 24. Li, C., Duan, W., Yang, F., and Zhang, X. (2006) Caveolin-3- anchored microdomains at the rabbit sarcoplasmic reticulum mem- branes. Biochem. Biophys. Res. Commun. 344, 1135–1140. 25. Lohn, M., Furstenau, M., Sagach, V., Elger, M., Schulze, W., Luft, F. C., Haller, H., and Gollasch, M. (2000) Ignition of calcium sparks in arterial and cardiac muscle through caveolae. Circ. Res. 87, 1034–1039. 26. Isshiki, M., Ying, Y. S., Fujita, T., and Anderson, R. G. (2002) A molecular sensor detects signal transduction from caveolae in living cells. J. Biol. Chem. 277, 43389–43398. 27. Vassilopoulos, S., Brocard, J., Garcia, L., Marty, I., and Bouron, A. (2007) Retrograde regulation of store-operated calcium channels by the ryanodine receptor-associated protein triadin 95 in rat skeletal myotubes. Cell Calcium 41, 179–185. 28. Ampong, B. N., Imamura, M., Matsumiya, T., Yoshida, M., and Takeda, S. (2005) Intracellular localization of dysferlin and its association with the dihydropyridine receptor. Acta Myol. 24, 134–144. 29. Parton, R. G., Way, M., Zorzi, N., and Stang, E. (1997) Caveolin-3 associates with developing T-tubules during muscle differentiation. J. Cell Biol. 136, 137–154. 30. Hernandez-Deviez, D. J., Martin, S., Laval, S. H., Lo, H. P., Cooper, S. T., North, K. N., Bushby, K., and Parton, R. G. (2006) Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3. Hum. Mol. Genet. 15, 129–142. 31. Marty, I., Faure, J., Fourest-Lieuvin, A., Vassilopoulos, S., Oddoux, S., and Brocard, J. (2009) Triadin: What possible function 20 years later? J. Physiol. 587, 3117–3121. 32. Minetti, C., Sotgia, F., Bruno, C., Scartezzini, P., Broda, P., Bado, M., Masetti, E., Mazzocco, M., Egeo, A., Donati, M. A., Volonte, D., Galbiati, F., Cordone, G., Bricarelli, F. D., Lisanti, M. P., and Zara, F. (1998) Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nat. Genet. 18, 365–368. 33. Galbiati, F., Volonte, D., Minetti, C., Chu, J. B., and Lisanti, M. P. (1999) Phenotypic behavior of caveolin-3 mutations that cause auto- somal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of LGMD-1C caveolin-3 mutants within the golgi complex. J. Biol. Chem. 274, 25632–25641.