RAB3 AND SYNAPTOTAGMIN: The Yin and Yang of Synaptic Membrane Fusion

Abstract

▪ Abstract Synaptic vesicle exocytosis occurs in consecutive steps: docking, which specifically attaches vesicles to the active zone; priming, which makes the vesicles competent for Ca²⁺-triggered release and may involve a partial fusion reaction; and the final Ca²⁺-regulated step that completes fusion. Recent evidence suggests that the critical regulation of the last step in the reaction is mediated by two proteins with opposite actions: synaptotagmin, a Ca²⁺-binding protein that is essential for Ca²⁺-triggered release and probably serves as the Ca²⁺-sensor in fusion, and rab3, which limits the number of vesicles that can be fused as a function of Ca²⁺ in order to allow a temporally limited, repeatable signal.