PH-DEPENDENT INTERACTION OF AN INTRALUMINAL LOOP OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR WITH CHROMOGRANIN-A

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store role of the secretory vesicles of adrenal medullary chromaffin cells is attributed to the presence of high capacity, low affinity Ca2+ binding protein chromogranin A. Chromogranin A has recently been shown to interact with the protein component(s) on the intraluminal side of the secretory vesicle membrane at the intravesicular pH of 5.5 but to dissociate from them at the near physiological pH of 7.5. Further, one of the chromogranin A-interacting membrane proteins was tentatively identified as the IP3 receptor. Therefore, the pH-dependent potential interaction of the intraluminal loop domains of the IP3 receptor with chromogranin A was studied by analytical ultracentrifugation utilizing synthetic intraluminal loop peptides of the IP3 receptor labeled with 5-hydroxy-tryptophan at the N-terminus as a chromophore. One of the intraluminal loop domains was found to interact with chromogranin A at pH 5.5 but not at pH 7.5, suggesting the importance of the intraluminal loop domain in transmitting Ca2+ mobilization signals to chromogranin A.