Abstract
Inositol 1,4,5-trisphosphate (IP 3)-mediated calcium (Ca 2+) signaling is subject to cytosolic and luminal regulatory mechanisms. In Xenopus oocytes, Ca 2+-sensitive gating of the IP 3 receptor (IP 3R) produces repetitive waves of Ca 2+ release. We examined the role of the luminal Ca 2+-binding protein calreticulin (CRT) in IP 3-mediated Ca 2+ signaling by using Ca 2+ wave activity as a sensitive Ca 2+ release assay. Overexpression of CRT inhibited repetitive IP 3-induced Ca 2+ waves. Deletion mutagenesis demonstrated that CRT inhibition was mediated by the high affinity-low capacity Ca 2+-binding domain, which contributes little to Ca 2+ storage. This novel function of CRT in intracellular Ca 2+ signaling may be regulated by Ca 2+ occupancy of the high affinity binding site.
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