Calcium-induced degradation of the inositol (1,4,5)-trisphosphate receptor/Ca(2+)-channel

Ca(2+)-induced degradation of the neuronal inositol (1,4,5)-trisphosphate receptor, a protein which regulates Ca(2+)-release from intracellular stores, has been examined. The IP3-receptor, immunopurified from rat cerebellum, appeared to be an excellent substrate for purified Ca(2+)-activated neutral protease (calpain). Incubation of membranes or immunopurified IP3-receptor with Ca2+ and cerebellar cytosol also resulted in degradation of the receptor. Two main fragments with approximate molecular masses of 130 and 95 kDa were generated, both of which appeared to derive from the carboxyterminal Ca(2+)-channel-containing part of the protein. These data suggest that activation of the IP3-receptor, by causing increases in intracellular [Ca2+], might result in degradation of the N-terminal, IP3-binding part of the receptor.