Emerging Roles of Presynaptic Proteins in Ca ++ -Triggered Exocytosis

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Abstract
Molecules involved in late steps of neurotransmitter release at the synapse can be examined by noting the two speeds of the components of the exocytotic burst that are triggered by an increase in free Ca ++ . From studies of Ca ++ -dependent exocytosis of large dense-core vesicles in chromaffin cells, it seems that initiation of the SNARE complex is the molecular event underlying the priming process and that Munc13 acts as a priming factor by opening syntaxin. If synaptic mechanisms are similar, much could be learned from the molecular and kinetic studies that can be performed in chromaffin cells. The twinning of techiques from biophysics and molecular biology has led to remarkable progress in understanding the molecular mechanisms of synaptic transmission. Here we review the current picture of Ca ++ -triggered exocytosis, which has emerged from studies of a simple cellular model, the adrenal chromaffin cell. We discuss the molecular players that have been assigned a specific role in a particular step of this process and give a brief outlook on what these insights might tell us about mechanisms of short-term plasticity at classical synapses.