CALCIUM-INDUCED DEGRADATION OF THE INOSITOL (1,4,5)-TRISPHOSPHATE RECEPTOR CA2-CHANNEL()

Ca2+-induced degradation of the neuronal inositol (1,4,5)-trisphosphat e receptor, a protein which regulates Ca2+-release from intracellular stores, has been examined. The IP3-receptor, immunopurified from rat c erebellum, appeared to be an excellent substrate for purified Ca2+-act ivated neutral protease (calpain). Incubation of membranes or immunopu rified IP3-receptor with Ca2+ and cerebellar cytosol also resulted in degradation of the receptor. Two main fragments with approximate molec ular masses of 130 and 95 kDa were generated, both of which appeared t o derive from the carboxyterminal Ca2+-channel-containing part of the protein. These data suggest that activation of the IP3-receptor, by ca using increases in intracellular [Ca2+], might result in degradation o f the N-terminal, IP3-binding part of the receptor.