Mechanism of action of the calpain activator protein in rat skeletal muscle.
Rat skeletal muscle contains a calpain activator protein characterized by a high specificity for calpain II, the high Ca(2+)-requiring isoform of this class of proteinases. The activator protein increases the rate of intramolecular conversion of the native 80-kDa catalytic subunit of calpain into the autolysed 75-kDa forms with maximal rate at concentrations of calcium approximately 25 times lower than those required by the native proteinase. The activator protein interacts with native calpain II forming a 1:1 complex; interaction does not occur with the fully activated form, produced by autoproteolysis. Even after immobilization to membranes, the activator binds to calpain, which then undergoes sequential activation and release from its bound form. The activator is itself resistant to digestion by calpain II, whereas it increases the rate at which homologous calpastatin is degraded by the proteinase. Taken together, these results are indicative of the existence in rat skeletal muscle of an activating system specific for calpain II which is potentially involved in the regulation of the inhibitory efficiency of calpastatin, through modulation of its intracellular level.
Michetti
M
M
Institute of Biological Chemistry, University of Genoa, Italy.
Viotti
P L
PL
Melloni
E
E
Pontremoli
S
S
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000302:isolation & purification / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D007700:Kinetics; D009132:Muscles / Q000378:metabolism*; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats
D002135:Calcium-Binding Proteins; D011506:Proteins; C033668:calpastatin; D004492:Edetic Acid; D002154:Calpain; D002118:Calcium