Inositol 1,4,5-trisphosphate receptor/Ca(2+) channel modulatory role of chromogranins A and B

Abstract

The secretory granules function as the major IP(3)-sensitive intracellular Ca(2+) store of secretory cells. Recently it was found that the secretory granules contain three isoforms of inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+) channels and high-capacity, low-affinity Ca(2+) storage proteins chromogranins A (CgA) and B (CgB). The IP(3)R/Ca(2+) channel was shown to directly interact with CgA and CgB at the intragranular pH 5.5, and this coupling led to modulation of the IP(3)R/Ca(2+) channel activity by the coupled chromogranins. These results provide the molecular structural basis of the IP(3)-mediated Ca(2+) release mechanism of secretory granules.