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. 1993 Feb 15;290(Pt 1):191–197. doi: 10.1042/bj2900191

Site-directed activation of calpain is promoted by a membrane-associated natural activator protein.

F Salamino 1, R De Tullio 1, P Mengotti 1, P L Viotti 1, E Melloni 1, S Pontremoli 1
PMCID: PMC1132401  PMID: 8439288

Abstract

Human erythrocytes contain a calpain activator protein with a molecular mass of approx. 40 kDa. The activator is present in association with the plasma membrane and promotes expression of calpain activity at a concentration of Ca2+ close to physiological values. The initial step of the activating mechanism involves association of the activator with calpain, followed by autoproteolytic activation of the proteinase in the presence of 1 microM Ca2+, at a rate identical to that induced by 1 mM Ca2+. In a reconstituted system, the activator binds to erythrocyte membranes, but not to phospholipid vesicles, suggesting the participation of an intrinsic membrane protein(s). In its membrane-associated form the activator selectively binds calpain, thus favouring interaction of the proteinase with the inner surface of plasma membranes. These results further confirm the importance of a natural activator protein in promoting intracellular activation of calpain under physiological conditions through a site-directed mechanism, which explains the high specificity of the proteinase for membrane of cytoskeletal proteins.

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Selected References

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