CALRETICULIN INHIBITS REPETITIVE INTRACELLULAR CA2+ WAVES

Inositol 1,4,5-trisphosphate (IP3)-mediated calcium (Ca2+) signaling i s subject to cytosolic and luminal regulatory mechanisms. In Xenopus o ocytes, Ca2+-sensitive gating of the IP3 receptor (IP(3)R) produces re petitive waves of Ca2+ release. We examined the role of the luminal Ca 2+-binding protein calreticulin (CRT) in IP3-mediated Ca2+ signaling b y using Ca2+ wave activity as a sensitive Ca2+ release assay. Overexpr ession of CRT inhibited repetitive IP3-induced Ca2+ waves. Deletion mu tagenesis demonstrated that CRT inhibition was mediated by the high af finity-low capacity Ca2+-binding domain, which contributes little to C a2+ storage. This novel function of CRT in intracellular Ca2+ signalin g may be regulated by Ca2+ occupancy of the high affinity binding site .