Rab3A Small G Protein and Its Regulators in Neurotransmitter Release and Synaptic Plasticity
Rab3A is a member of the Rab3 small GTP-binding protein (G protein) subfamily along with Rab3B., 3C., and 3D, and the Rab3 proteins belong to the Rab family (Takai et al., 2001). The Rab family members are involved in vesicle trafficking, such as exocytosis and endocytosis (Takai et al., 2001). Evidence is accumulating that Rab3A is involved in Ca2+-dependent exocytosis, particularly neurotransmitter release from nerve terminals (Takai et al., 2001). The Ca2+-dependent neurotransmitter release is regulated by several steps: translocation of synaptic vesicles from the reserve pool to the active zone of the presynaptic plasm membrane where Ca2+ channels localize, docking of the vesicles to the active zone, transition from the docking to the priming of the vesicles in the readily releasable pool, and fusion of the vesicles with the plasma membrane induced by Ca2+ influx (Fig. 1) (Takai et al., 2001). Studies on Rab3A knockout mice have revealed that Rab3A is not essential for basal neurotransmitter release but modulates synaptic plasticity (Geppert et al.,1994; 1997; Castillo et al., 1997). In Rab3A knockout mice, synaptic depression is increased during repetitive stimulation in the CA1 region of the hippocampus (Geppert et al., 1994), and mossy fiber long-term potentiation (LTP) in the CA3 region is abolished (Castillo et al., 1997). In cultured hippocampal neurons derived from Rab3A knockout mice, release probability is increased, while the size of the readily releasable pool measured by hypertonic solution is normal (Geppert et al., 1997). Rab3A appears to up-regulate the steps of the translocation and docking as well as to down-regulate the step of the fusion.
KeywordsKnockout Mouse Synaptic Vesicle Active Zone Neurotransmitter Release Vesicle Trafficking
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