1. Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Gottingen, Germany
2. Molecular Neurobiology Laboratory and Howard Hughes Medical Institute, The Salk Institute, La Jolla, California92037, USA
3. Department of Molecular Genetics and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas75235, USA

Correspondence to: Yukiko Goda Correspondence should be addressed to Y.G. (e-mail: Email: ygoda@jeeves.ucsd.edu).

Abstract

The Rab family of low-molecular-mass GTP-binding proteins are thought to guide membrane fusion between a transport vesicle and the target membrane, and to determine the specificity of docking^{1, 2, 3}. The docking and fusion of vesicles is, however, a complex multistep reaction, and the precise point at which Rab proteins act in these sequential processes is unknown. In brain, the Rab protein Rab3A is specific to synaptic vesicles, whose exocytosis can be monitored with submillisecond resolution by following synaptic transmission. We have now determined the precise point at which Rab3A acts in the sequence of synaptic vesicle docking and fusion by using electrophysiological analysis of neurotransmitter release in Rab3A-deficient mice. Unexpectedly, the size of the readily releasable pool of vesicles is normal, whereas Ca²⁺-triggered fusion is altered in the absence of Rab3A in that a more-than-usual number of exocytic events occur within a brief time after arrival of the nerve impulse.