pH-dependent interaction of chromogranin A with integral membrane proteins of secretory vesicle including 260-kDa protein reactive to inositol 1,4,5-triphosphate receptor antibody.

Chromogranin A is a high capacity, low affinity Ca(2+)-binding protein suggested to be responsible for the Ca2+ storage function of the secretory vesicle, which has been identified as a major inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ store of adrenal medullary chromaffin cells. Moreover, chromogranin A has recently been shown to interact with the vesicle membrane at the intravesicular pH of 5.5 and to be released from it at a near physiological pH of 7.5 (Yoo, S. H. (1993) Biochemistry 32, 8213-8219). In the present study, chromogranin A is shown to interact with several integral membrane proteins of secretory vesicles at pH 5.5 but not at pH 7.5. One of the chromogranin A-interacting membrane proteins had a mass of 260 kDa and reacted with the IP3 receptor antibody. This result suggested not only the existence of the IP3 receptor in the vesicle membrane but also the existence of direct communication between chromogranin A and the IP3 receptor. In addition, the pH-dependent interaction of chromogranin A with integral membrane proteins implies an important role for chromogranin A in the sorting process of the vesicle membrane proteins during vesicle biogenesis in the trans-Golgi network.