Advertisement

Skeletal Muscle-Specific Calpain, p94, and Connectin/Titin: Their Physiological Functions and Relationship to Limb-Girdle Muscular Dystrophy Type 2A

  • Hiroyuki Sorimachi
  • Yasuko Ono
  • Koichi Suzuki
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 481)

Abstract

The skeletal muscle-specific calpain homologue, p94 (also called calpain 3), is essential for normal muscle function. A mutation of the p94 gene causes limb-girdle muscular dystrophy type 2A (LGMD2A), which is one type of autosomal recessive inherited disease characterized by progressive muscular degeneration. In myofibrils, p94 specifically binds to connectin/ titin, and the activity of p94 is probably suppressed by this binding. Thus, we postulate that a signal transduction pathway exists, involving p94 and connectin/titin to modulate functions of skeletal muscle, and LGMD2A occurs when this signalling pathway is not properly regulated by p94. LGMD2A mutants of p94 also reveal significant information on the factors that relate structure to function in this molecule.

Keywords

Muscular Dystrophy Congenital Muscular Dystrophy Autolytic Activity PEVK Region Calpain Homologue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Banik NL, Shields DC, Ray S, Davis B, Matzelle D, Wilford G, Hogan EL. Role of calpain in spinal cord injury: effects of calpain and free radical inhibitors. Ann N Y Acad Sci 1998;844:131–37.PubMedCrossRefGoogle Scholar
  2. Barnes TM, Hodgkin J. The tra-3 sex determination gene of Caenorhabditis elegansencodes a member of the calpain regulatory protease family. EMBO J 1996;15:4477–84.PubMedGoogle Scholar
  3. Bartoloni L, Horrigan SK, Viles KD, Gilchrist JM, Stajich JM, Vance JM, Yamaoka LH, Pericak-Vance MA, Westbrook CA, Speer MC. Use of a CEPH meiotic breakpoint panel to refine the locus of limb-girdle muscular dystrophy type 1A (LGMD1A) to a 2-Mb interval on 5q31. Genomics. 1998;54:250–55.PubMedCrossRefGoogle Scholar
  4. Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, Richard I, Marchand S, Bourg N, Argov Z, Sadeh M, Mahjneh I, Marconi G, Passos-Bueno MR, Moreira E de S, Zatz M, Beckmann JS, Bushby K. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 1998;20:37–42.PubMedCrossRefGoogle Scholar
  5. Beckmann JS, Bushby KM. Advances in the molecular genetics of the limb-girdle type of autosomal recessive progressive muscular dystrophy. Curr Opin Neurol 1996;9:389–93.PubMedCrossRefGoogle Scholar
  6. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet 1994;8:323–27.PubMedCrossRefGoogle Scholar
  7. Bonne G, Di Barletta MR, Varnous S, Bécane HM, Hammouda EH, Merlini L, Muntoni F, Greenberg CR, Gary F, Urtizberea JA, Duboc D, Fardeau M, Toniolo D, Schwartz K. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet 1999;21:285–88.PubMedCrossRefGoogle Scholar
  8. Bönnemann CG, McNally EM, Kunkel LM. Beyond dystrophin: current progress in the muscular dystrophies. Curr Opin Pediatr 1996;8:569–82.PubMedCrossRefGoogle Scholar
  9. Bönnemann CG, Modi R, Noguchi S, Mizuno Y, Yoshida M, Gussoni E, McNally EM, Duggan DJ, Angelini C, Hoffman EP Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex. Nat Genet 1995;11:266–73.PubMedCrossRefGoogle Scholar
  10. Brais B, Bouchard JP, Xie YG, Rochefort DL, Chrétien N, Tome FM, Lafrenière RG, Rommens JM, Uyama E, Nohira O, Blumen S, Korczyn AD, Heutink P, Mathieu J, Duranceau A, Codère F, Fardeau M, Rouleau GA. Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet 1998;18:164–67.PubMedCrossRefGoogle Scholar
  11. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hunter K, Stanton VP, Thirion JP, Hudson T, Sohn R, Zemelman B, Snell RG, Rundle SA, Crow S, Davies J, Shelbourne P, Buxton J, Jones C, Juvnen V, Johnson K, Harper PS, Shaw DJ, Housman DE. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 1992;68:799–808.PubMedCrossRefGoogle Scholar
  12. Carafoli E, Molinari M. Calpain: a protease in search of a function? Biochem Biophys Res Commun 1998;247:193–03.PubMedCrossRefGoogle Scholar
  13. Cox GF, Kunkel LM. Dystrophies and heart disease. Curr Opin Cardiol 1997;12;329–43.PubMedCrossRefGoogle Scholar
  14. Denison SH, Orejas M, Arst HN Jr. Signalling of ambient pH in Aspergillusinvolves a cysteine protease. J Biol Chem 1995;270:28519–22.PubMedCrossRefGoogle Scholar
  15. Emery AEH. The muscular dystrophies. BMJ 1998;317:991–95.PubMedCrossRefGoogle Scholar
  16. Futai E, Maeda T, Sorimachi H, Kitamoto K, Ishiura S, Suzuki K. The protease activity of a calpain-like cysteine protease in Saccharomyces cerevisiaeis required for alkaline adaptation and sporulation. Mol Gen Genet 1999;260:559–68.PubMedCrossRefGoogle Scholar
  17. Haravuori H, Mäkelä-Bengs P, Udd B, Partanen J, Pulkkinen L, Somer H, Peltonen L. Assignment of the tibial muscular dystrophy locus to chromosome 2q31. Am J Hum Genet 1998;62:620–26.PubMedCrossRefGoogle Scholar
  18. Helbling-Leclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, Tomé FM, Schwartz K, Fardeau M, Tryggvason K, Guicheney P. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet 1995;11:216–18.PubMedCrossRefGoogle Scholar
  19. Herasse M, Ono Y, Fougerousse F, Kimura E, Stockholm D, Beley C, Montarras D, Pinset C, Sorimachi H, Suzuki K, Beckmann JS, Richard I. Expression and functional characteristics of calpain 3 isoforms generated through tissue-specific transcriptional and posttranscriptional events. Mol Cell Biol 1999;19:4047–55.PubMedGoogle Scholar
  20. Hoffman EP, Knudson CM, Campbell KP, Kunkel LM. Subcellular fractionation of dystrophin to the triads of skeletal muscle. Nature 1987;330:754–758.PubMedCrossRefGoogle Scholar
  21. Johnson GV, Guttmann RP Calpains: intact and active? Bioessays 1997;19:101–8.CrossRefGoogle Scholar
  22. Kinbara K, Sorimachi H, Ishiura S, Suzuki K. Muscle-specific calpain, p94, interacts with the extreme C-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs. Arch Biochem Biophys 1997;342:99–107.PubMedCrossRefGoogle Scholar
  23. Kobayashi K, Nakahori Y, Miyake M, Matsumura K, Kondo-Iida E, Nomura Y, Segawa M, Yoshioka M, Saito K, Osawa M, Hamano K, Sakakihara Y, Nonaka I, Nakagome Y, Kanazawa I, Nakamura Y, Tokunaga K, Toda T. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 1998;394:388–92.PubMedCrossRefGoogle Scholar
  24. Lim LE, Campbell KP. The sarcoglycan complex in limb-girdle muscular dystrophy. Curr Opin Neurol 1998;11:443–52.PubMedCrossRefGoogle Scholar
  25. Lim LE, Duclos F, Broux O, Bourg N, Sunada Y, Allamand V, Meyer J, Richard I, Moomaw C, Slaughter C, Tome FMS, Fardeau M, Jackson CE, Beckmann JS, Campbell KP. Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4ql2. Nat Genet 1995;11:257–65.PubMedCrossRefGoogle Scholar
  26. Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea JA, Hentati F, Hamida MB, Bohlega S, Culper EJ, Amato AA, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler BA, Schurr E, Arahata K, de Jong PJ, Brown RH Jr. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb-girdle muscular dystrophy. Nat Genet 1998;20:31–36.PubMedCrossRefGoogle Scholar
  27. Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P, Bado M, Masetti E, Mazzocco M, Egeo A, Donati MA, Volonté D, Galbiati F, Cordone G, Bricarelli FD, Lisanti MP, Zara F. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nat Genet 1998;18:365–68.PubMedCrossRefGoogle Scholar
  28. Moreira ES, Vainzof M, Marie SK, Sertié AL, Zatz M, Passos-Bueno MR. The seventh form of autosomal recessive limb-girdle muscular dystrophy is mapped to 17q11–12. Am J Hum Genet 1997;61:151–59.PubMedCrossRefGoogle Scholar
  29. Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R, Hayashi YK, Tsukahara T, Arahata K. Ernenn deficiency at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy. Nat Genet 1996;12:254–59.PubMedCrossRefGoogle Scholar
  30. Nigro V, de Sá Moreira E, Piluso G, Vainzof M, Belsito A, Politano L, Puca AA, Passos-Bueno MR, Zatz M. Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene. Nat Genet 1996;14:195–98.PubMedCrossRefGoogle Scholar
  31. Noguchi S, McNally EM, Ben Othmane K, Hagiwara Y, Mizuno Y, Yoshida M, Yamamoto H, Bönnemann CG, Gussoni E, Denton PH, Kyriakides T, Middleton L, Hentati F, Hamida MB, Nonaka I, Vance JM, Kunkel LM, Ozawa E. Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. Science 1995;270:819–22.PubMedCrossRefGoogle Scholar
  32. Ono Y, Sorimachi H, Suzuki K. Structure and physiology of calpain, an enigmatic protease. Biochem Biophys Res Commun 1998a;245:289–94.PubMedCrossRefGoogle Scholar
  33. Ono Y, Shimada H, Sorimachi H, Richard I, Saido T C, Beckmann J S, Ishiura S, Suzuki K. Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A (LGMD2A). J Biol Chem 1998b;273:17073–78.PubMedCrossRefGoogle Scholar
  34. Ozawa E, Noguchi S, Mizuno Y, Hagiwara Y, Yoshida M. From dystrophinopathy to sarcoglycanopathy: evolution of a concept of muscular dystrophy. Muscle Nerve 1998;21:421–38.PubMedCrossRefGoogle Scholar
  35. Ranum LP, Rasmussen PF, Benzow KA, Koob MD, Day JW. Genetic mapping of a second myotonic dystrophy locus. Nat Genet 1998;19:196–98.PubMedCrossRefGoogle Scholar
  36. Richard I, Broux O, Allamand V, Fougerousse F, Chiannilkulchai N, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C, Hillaire D, Passos-Bueno M-R, Zatz M, Tischfield JA, Fardeau M, Jackson CE, Cohen D, Beckmann JS. Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell 1995;81:27–40.PubMedCrossRefGoogle Scholar
  37. Richard I, Roudaut C, Saenz A, Pogue R, Grimbergen J E M A, Beley C, Cobo A-M, de Diego C, Eymard B, Gallano P, Ginjaar H B, Lasa A, Pollitt C, Topaloglu H, de Visser M, van der Kooi A, Bushby K, Bakker E, Lopez de Munain A, Fardeau M, and Beckmann J S. Calpainopathy — A survey of mutations and polymorphisms. Am J Hum Genet 1999;64:1524–40.PubMedCrossRefGoogle Scholar
  38. Roberds SL, Leturcq F, Allamand V, Piccolo F, Jeanpierre M, Anderson RD, Lim LE, Lee JC, Tomé FMS, Romero NB, Fardeau M, Beckmann JS, Kaplan J-C, Campbell KP. Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy. Cell 1994;78:625–33.PubMedCrossRefGoogle Scholar
  39. Sorimachi H, Imajoh-Ohmi S, Emori Y, Kawasaki H, Ohno S, Minami Y, Suzuki K. Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m-and μ-types. Specific expression of the mRNA in skeletal muscle. J Biol Chem 1989;264:20106–11.PubMedGoogle Scholar
  40. Sorimachi H, Toyama-Sorimachi N, Saido TC, Kawasaki H, Sugita H, Miyasaka M, Arahata K, Ishiura S, Suzuki K. Muscle-specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle. J Biol Chem 1993;268:10593–605.PubMedGoogle Scholar
  41. Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K, Suzuki K. Muscle-specific calpain, p94, responsible for limb-girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence. J Biol Chem 1995;270:31158–62.PubMedCrossRefGoogle Scholar
  42. Sorimachi H, Ishiura S, Suzuki K. Structure and physiological function of calpains. Biochem J 1997;328:721–32.PubMedGoogle Scholar
  43. Suzuki K, Sorimachi H. A novel aspect of calpain activation. FEBS Lett 1998;433:1–4.PubMedCrossRefGoogle Scholar
  44. Tsuchiya Y, Arahata K. Emery-Dreifuss syndrome. Curr Opin Neurol 1997;10:421–25.PubMedCrossRefGoogle Scholar
  45. van der Kooi AJ, van Meegen M, Ledderhof TM, McNally EM, de Visser M, Bolhuis PA. Genetic localization of a newly recognized autosomal dominant limb-girdle muscular dystrophy with cardiac involvement (LGMD1B) to chromosome lq11–21. Am J Hum Genet 1997;60:891–95.PubMedGoogle Scholar
  46. Weiler T, Greenberg CR, Zelinski T, Nylen E, Coghlan G, Crumley MJ, Fujiwara TM, Morgan K, Wrogemann K. A gene for autosomal recessive limb-girdle muscular dystrophy in Manitoba Hutterites maps to chromosome region 9q31-q33: evidence for another limb-girdle muscular dystrophy locus. Am J Hum Genet 1998;63:140–47.PubMedCrossRefGoogle Scholar
  47. Wijmenga C, Hewitt JE, Sandkuijl LA, Clark LN, Wright TJ, Dauwerse HG, Gruter AM, Hofker MH, Moerer P, Williamson R, et al. Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy. Nat Genet 1992;2:26–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Hiroyuki Sorimachi
    • 1
  • Yasuko Ono
    • 1
  • Koichi Suzuki
    • 1
  1. 1.Department of Molecular Biology, Institute of Molecular and Cellular BiosciencesThe University of TokyoYayoi, Bunkyo-ku, TokyoJapan

Personalised recommendations