Calpain 3: a key regulator of the sarcomere?

Stephanie Duguez, Marc Bartoli, Isabelle Richard

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Calpain 3 is a 94-kDa calcium-dependent cysteine protease mainly expressed in skeletal muscle. In this tissue, it localizes at several regions of the sarcomere through binding to the giant protein, titin. Loss-of-function mutations in the calpain 3 gene have been associated with limb-girdle muscular dystrophy type 2A (LGMD2A), a common form of muscular dystrophy found world wide. Recently, significant progress has been made in understanding the mode of regulation and the possible function of calpain 3 in muscle. It is now well accepted that it has an unusual zymogenic activation and that cytoskeletal proteins are one class of its substrates. Through the absence of cleavage of these substrates, calpain 3 deficiency leads to abnormal sarcomeres, impairment of muscle contractile capacity, and death of the muscle fibers. These data indicate a role for calpain 3 as a chef d'orchestre in sarcomere remodeling and suggest a new category of LGMD2 pathological mechanisms.
LanguageEnglish
Pages3427-3436
JournalThe FEBS journal
Volume273
Issue number15
DOIs
Publication statusPublished - 17 Jul 2006

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Sarcomeres
Calpain
Muscle
Muscles
Connectin
Cytoskeletal Proteins
Cysteine Proteases
Muscular Dystrophies
Substrates
Skeletal Muscle
Genes
Chemical activation
Tissue
Calcium
Mutation
Fibers
Proteins

Keywords

  • LGMD2A
  • calpain 3

Cite this

Duguez, Stephanie ; Bartoli, Marc ; Richard, Isabelle. / Calpain 3: a key regulator of the sarcomere?. In: The FEBS journal. 2006 ; Vol. 273, No. 15. pp. 3427-3436.
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Calpain 3: a key regulator of the sarcomere? / Duguez, Stephanie; Bartoli, Marc; Richard, Isabelle.

In: The FEBS journal, Vol. 273, No. 15, 17.07.2006, p. 3427-3436.

Research output: Contribution to journalArticle

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AU - Richard, Isabelle

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AB - Calpain 3 is a 94-kDa calcium-dependent cysteine protease mainly expressed in skeletal muscle. In this tissue, it localizes at several regions of the sarcomere through binding to the giant protein, titin. Loss-of-function mutations in the calpain 3 gene have been associated with limb-girdle muscular dystrophy type 2A (LGMD2A), a common form of muscular dystrophy found world wide. Recently, significant progress has been made in understanding the mode of regulation and the possible function of calpain 3 in muscle. It is now well accepted that it has an unusual zymogenic activation and that cytoskeletal proteins are one class of its substrates. Through the absence of cleavage of these substrates, calpain 3 deficiency leads to abnormal sarcomeres, impairment of muscle contractile capacity, and death of the muscle fibers. These data indicate a role for calpain 3 as a chef d'orchestre in sarcomere remodeling and suggest a new category of LGMD2 pathological mechanisms.

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