Calpain 3: a key regulator of the sarcomere?

FEBS J. 2006 Aug;273(15):3427-36. doi: 10.1111/j.1742-4658.2006.05351.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calpain / chemistry
  • Calpain / genetics
  • Calpain / physiology*
  • Gene Expression
  • Humans
  • Hydrolysis
  • Molecular Structure
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • Sarcomeres / physiology*
  • Subcellular Fractions / enzymology
  • Substrate Specificity

Substances

  • Muscle Proteins
  • CAPN3 protein, human
  • Calpain