Is calpain activity regulated by membranes and autolysis or by calcium and calpastatin?
Although the Ca(2+)-dependent proteinase (calpain) system has been found in every vertebrate cell that has been examined for its presence and has been detected in Drosophila and parasites, the physiological function(s) of this system remains unclear. Calpain activity has been associated with cleavages that alter regulation of various enzyme activities, with remodeling or disassembly of the cell cytoskeleton, and with cleavages of hormone receptors. The mechanism regulating activity of the calpain system in vivo also is unknown. It has been proposed that binding of the calpains to phospholipid in a cell membrane lowers the Ca2+ concentration, [Ca2+], required for the calpains to autolyze, and that autolysis converts an inactive proenzyme into an active protease. Recent studies, however, show that the calpains bind to specific proteins and not to phospholipids, and that binding to cell membranes does not affect the [Ca2+] required for autolysis. It seems likely that calpain activity is regulated by binding of Ca2+ to specific sites on the calpain molecule, with binding to each site eliciting a response (proteolytic activity, calpastatin binding, etc.) specific for that site. Regulation must also involve an, as yet, undiscovered mechanism that increases the affinity of the Ca(2+)-binding sites for Ca2+.
Goll
D E
DE
Muscle Biology Group, University of Arizona, Tucson 85721.
Thompson
V F
VF
Taylor
R G
RG
Zalewska
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002154:Calpain / Q000502:physiology*; D002384:Catalysis; D002462:Cell Membrane / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D007448:Invertebrates / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014714:Vertebrates / Q000378:metabolism
D002135:Calcium-Binding Proteins; D008563:Membrane Lipids; D010743:Phospholipids; D011956:Receptors, Cell Surface; C033668:calpastatin; D002154:Calpain; D002118:Calcium