Inositol 1,4,5-trisphosphate receptor/Ca2+ channel modulatory role of chromogranin A, a Ca2+ storage protein of secretory granules

The secretory granules of neuroendocrine cells, which contain large amounts of Ca2+ and chromogranins, have been demonstrated to release Ca2+ in respo nse to inositol 1,4,5-trisphosphate (IP3), indicating the IP3-sensitive int racellular Ca2+ store role of secretory granules. In our previous study, ch romogranin A (CGA) was shown to interact with several secretory granule mem brane proteins, including the IP3 receptor (IP3R), at the intravesicular pH 5.5 (Yoo, S. H, (1994) J, Biol, Chem, 269, 12001-12006); To examine the fu nctional aspect of this coupling, we measured the IP3-mediated Ca2+ release property of the IP3R reconstituted into liposomes in the presence and abse nce of CGA. Presence of CGA in the IP3R-reconstituted liposome significantl y enhanced the IP3-mediated Ca2+ release from the liposomes, Moreover, the number of IP3 bound to the reconstituted IP3R increased. The fluorescence e nergy transfer and IP3R Trp fluorescence quenching studies indicated that t he structure of reconstituted IP3R becomes more ordered and exposed in the presence of CGA, suggesting that the coupled CGA in the liposome caused str uctural changes of the IP3R, changing it to a structure that is better suit ed to IF, binding and subsequent Ca2+ release, These results appear to unde rscore the physiological significance of IP3R-CGA coupling in the secretory granules.