Role of secretory granules in inositol 1,4,5-trisphosphate-dependent Ca(2+) signaling: from phytoplankton to mammals.

The majority of secretory cell calcium is stored in secretory granules that serve as the major IP(3)-dependent intracellular Ca(2+) store. Even in unicellular phytoplankton secretory granules are responsible for the IP(3)-induced Ca(2+) release that triggers exocytosis. The number of secretory granules in the cell is directly related not only to the magnitude of IP(3)-induced Ca(2+) release, which accounts for the majority of the IP(3)-induced cytoplasmic Ca(2+) release in neuroendocrine cells, but also to the IP(3) sensitivity of the cytoplasmic IP(3) receptor (IP(3)R)/Ca(2+) channels. Moreover, secretory granules contain the highest IP(3)R concentrations and the largest amounts of IP(3)Rs in any subcellular organelles in neuroendocrine cells. Secretory granules from phytoplankton to mammals contain large amounts of polyanionic molecules, chromogranins being the major molecules in mammals, in addition to acidic intragranular pH and high Ca(2+) concentrations. The polyanionic molecules undergo pH- and Ca(2+)-dependent conformational changes that serve as a molecular basis for condensation-decondensation phase transitions of the intragranular matrix. Likewise, chromogranins undergo pH- and Ca(2+)-dependent conformational changes with increased exposure of the structure and increased interactions with Ca(2+) and other granule components at acidic pH. The unique physico-chemical properties of polyanionic molecules appear to be at the center of biogenesis, and physiological functions of secretory granules in living organisms from primitive to advanced species.