The Calpain System
Muscle Biology Group, University of Arizona, Tucson, Arizona Goll, Darrel E., Valery F. Thompson, Hongqi Li, Wei Wei, and Jinyang Cong. The Calpain System. Physiol Rev 83: 731801, 2003; 10.1152/physrev.00029.2002.The calpain system originally comprised three molecules: two Ca 2+ -dependent proteas...
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Published in | Physiological reviews Vol. 83; no. 3; pp. 731 - 801 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Am Physiological Soc
01.07.2003
American Physiological Society |
Subjects | |
Online Access | Get full text |
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Summary: | Muscle Biology Group, University of Arizona, Tucson, Arizona
Goll, Darrel E., Valery F. Thompson, Hongqi Li, Wei Wei, and Jinyang Cong. The Calpain System. Physiol Rev 83: 731801, 2003; 10.1152/physrev.00029.2002.The calpain system originally comprised three molecules: two Ca 2+ -dependent proteases, µ-calpain and m-calpain, and a third polypeptide, calpastatin, whose only known function is to inhibit the two calpains. Both µ- and m-calpain are heterodimers containing an identical 28-kDa subunit and an 80-kDa subunit that shares 5565% sequence homology between the two proteases. The crystallographic structure of m-calpain reveals six "domains" in the 80-kDa subunit: 1 ) a 19-amino acid NH 2 -terminal sequence; 2 ) and 3 ) two domains that constitute the active site, IIa and IIb; 4 ) domain III; 5 ) an 18-amino acid extended sequence linking domain III to domain IV; and 6 ) domain IV, which resembles the penta EF-hand family of polypeptides. The single calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca 2+ dependent. Since 1989, cDNA cloning has identified 12 additional mRNAs in mammals that encode polypeptides homologous to domains IIa and IIb of the 80-kDa subunit of µ- and m-calpain, and calpain-like mRNAs have been identified in other organisms. The molecules encoded by these mRNAs have not been isolated, so little is known about their properties. How calpain activity is regulated in cells is still unclear, but the calpains ostensibly participate in a variety of cellular processes including remodeling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca 2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma.
Address for reprint requests and other correspondence: D. E. Goll, Muscle Biology Group, Univ. of Arizona, Tucson, AZ 85721 (E-mail: darrel.goll{at}arizona.edu ). |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-Review-3 content type line 23 ObjectType-Feature-3 ObjectType-Review-1 |
ISSN: | 0031-9333 1522-1210 |
DOI: | 10.1152/physrev.00029.2002 |