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Vol. 12, Issue 10, 3095-3102, October 2001

Rab3A Is Involved in Transport of Synaptic Vesicles to the Active Zone in Mouse Brain Nerve Terminals

A.G. Miriam Leenders,^* Fernando H. Lopes da Silva,^* Wim E.J.M. Ghijsen,^* and Matthijs Verhage^§

 ^*Graduate School for the Neurosciences, Institute of Neurobiology, University of Amsterdam, 1098 SM The Netherlands,  Molecular Neuroscience, R. Magnus Institute, University of Utrecht Medical Center, 3584 CG Utrecht, The Netherlands

The rab family of GTP-binding proteins regulates membrane transport between intracellular compartments. The major rab protein in brain, rab3A, associates with synaptic vesicles. However, rab3A was shown to regulate the fusion probability of synaptic vesicles, rather than their transport and docking. We tested whether rab3A has a transport function by analyzing synaptic vesicle distribution and exocytosis in rab3A null-mutant mice. Rab3A deletion did not affect the number of vesicles and their distribution in resting nerve terminals. The secretion response upon a single depolarization was also unaffected. In normal mice, a depolarization pulse in the presence of Ca²⁺ induces an accumulation of vesicles close to and docked at the active zone (recruitment). Rab3A deletion completely abolished this activity-dependent recruitment, without affecting the total number of vesicles. Concomitantly, the secretion response in the rab3A-deficient terminals recovered slowly and incompletely after exhaustive stimulation, and the replenishment of docked vesicles after exhaustive stimulation was also impaired in the absence of rab3A. These data indicate that rab3A has a function upstream of vesicle fusion in the activity-dependent transport of synaptic vesicles to and their docking at the active zone.

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Present address: Department of Neurogenomics, Free University Amsterdam, de Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.

^§ Corresponding author. E-mail address: m.verhage{at}med.uu.nl or ghijsen{at}bio.uva.nl.

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Molecular Biology of the Cell
Vol. 12, 3095-3102, October 2001
Copyright © 2001 by The American Society for Cell Biology

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