Functional Defects of a Muscle-specific Calpain, p94, Caused by Mutations Associated with Limb-Girdle Muscular Dystrophy Type 2A*

p94 (calpain3), a muscle-specific member of the calpain family, has been shown to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A), a form of autosomal recessive and progressive neuromuscular disorder. To elucidate the molecular mechanism of LGMD2A, we constructed nine p94 missense point mutants found in LGMD2A and analyzed their p94 unique properties. All mutants completely or almost completely lose the proteolytic activity against a potential substrate, fodrin. However, some of the mutants still possess autolytic activity and/or connectin/titin binding ability, indicating these properties are not necessary for the LGMD2A phenotypes. These results provide strong evidence that LGMD2A results from the loss of proteolysis of substrates by p94, suggesting a novel molecular mechanism leading to muscular dystrophies.

• Publication year

  1998

• Venue

  Journal of Biological Chemistry

• Publication date

  1998-07-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.273.27.17073PMID 9642272
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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