Calmodulin is the divalent cation receptor for rapid endocytosis, but not exocytosis, in adrenal chromaffin cells

Exocytosis and the ensuing rapid endocytosis in adrenal chromaffin cells are both Ca2+-dependent phenomena but differ in their divalent cation specificity, implying distinct Ca2+ receptors for the two processes. To ascertain whether calmodulin is the Ca2+ receptor for either process, we blocked its function by introducing calmodulin-binding peptides or anti-calmodulin antibodies into these cells. Exo/endocytosis was followed by measurement of cell membrane capacitance. Rapid endocytosis, but not exocytosis, was abolished by these treatments, indicating that calmodulin is the Ca2+ receptor for rapid endocytosis but is not involved in exocytosis. The principal calmodulin target is not protein phosphatase-as, as antagonism of this enzyme did not inhibit but accelerated rapid endocytosis. Calmodulin may thus regulate both the rate and extent of rapid endocytosis by distinct pathways.