Tyrosine phosphorylation regulates rapid endocytosis in adrenal chromaffin cells.

Secretion of neurotransmitter at the synapse and in secretory cells depends on the availability of vesicles for exocytosis. Rapid endocytosis is responsible for initiating local vesicle recycling and is essential during sustained neurotransmission. Although exocytosis is triggered by Ca(2+) influx and modulated by serine/threonine kinases, relatively little is known about the regulation of rapid endocytosis. Our data suggest that rapid endocytosis is controlled by tyrosine phosphorylation. Treatment of bovine adrenal chromaffin cells with tyrphostin 23, a protein tyrosine kinase inhibitor, dramatically slowed the time course of rapid endocytosis. In contrast, there was no effect on either the amount or rate of exocytosis. Application of orthovanadate, Zn(2+), or poly(Glu, Tyr) (4:1), each of which is a tyrosine phosphatase inhibitor, reversed the effect of tyrphostin 23 on rapid endocytosis. Thus rapid endocytosis, like exocytosis, is subject to regulation by intracellular signaling pathways.