Calcium‐dependent proteases: an enzyme system active at cellular membranes?

Abstract

Proteases having a neutral pH optimum and an absolute requirement for calcium ion are found in virtually all mammalian cells. Association of calcium‐dependent proteases and a specific inhibitor protein with biological membranes seems to be an important regulatory feature of this proteolytic system, and it is likely that membranes are preferred sites for calcium‐dependent protease action. Several recent hypotheses for the physiological function of calcium‐dependent proteolysis are consistent with a membrane‐associated protease action. Calcium‐dependent proteases may participate in cell membrane fusion: the proteolysis of membrane proteins, which is required for the efficient fusion of erythrocytes, may be catalyzed by these enzymes. There is also evidence for the involvement of calcium‐dependent proteolysis in postsynaptic membrane remodeling in the hippocampus after long‐term potentiation. Although the relationship of the proteolysis to synaptic function is not known, it could have important physiological or pathophysiological consequences. Finally, it has recently been suggested that calcium‐dependent proteolysis may be a physiologically significant mechanism for activating membrane‐associated protein kinase C after exposure of some cell types to phorbol esters or other mitogens. Further pursuit of these hypotheses may reveal a novel role for intracellular calcium‐regulated proteolysis in membrane‐associated cell functions.— M ellgren , R. L. Calcium‐dependent proteases: an enzyme system active at cellular membranes? FASEB J. 1: 110‐115; 1987.