Rab3A Small G Protein and Its Regulators in Neurotransmitter Release and Synaptic Plasticity

  • Hiroyuki Nakanishi
  • Takuya Sasaki
  • Jun Miyoshi
  • Yoshimi Takai
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)

Abstract

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.

Keywords

Knockout Mouse Synaptic Vesicle Active Zone Neurotransmitter Release Vesicle Trafficking 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Castillo, P.E., Janz, R., Südhof, T.C., Tzounopoulos, T., Malenka, R.C., and Nicoll, R.A, 1997, Rab3A is essential for mossy fiber long-term potentiation in the hippocampus, Nature 388:590–593.PubMedCrossRefGoogle Scholar
  2. D’Adamo, P., Menegon, A., Lo Nigro, C., Grasso, M., Gulisano, M., Tamanini, F., Bienvenu, T., Gedeon, A.K., Oostra, B., Wu, S.K., Tandon, A., Valtorta, F., Balch, W.E., Chelly, J., Toniolo, D., 1998, Mutations in GDI1 are responsible for X-linked non-specific mental retardation. Nature Genet. 19:134–139.PubMedCrossRefGoogle Scholar
  3. Geppert, M., Bolshakov, V.Y., Siegelbaum, S.A., Takei, K., De Camilli, P., Hammer, R.E., and Südhof, T.C., 1994, The role of Rab3A in neurotransmitter release, Nature 369:493–497.PubMedCrossRefGoogle Scholar
  4. Geppert, M., Goda, Y., Stevens, CF., and Südhof, T.C., 1997, The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion., Nature 387:810–814.PubMedCrossRefGoogle Scholar
  5. Iwasaki, K., Staunton, J., Saifee, O., Nonet, M., and Thomas, J.H., 1997, aex-3 encodes a novel regulator of presynaptic activity in C. elegans. Neuron 18:613–622.PubMedCrossRefGoogle Scholar
  6. Takai, Y., Sasaki, T., Shirataki, H., and Nakanishi, H., 1996, Rab3A small GTP-binding protein in Ca2+-dependent exocytosis, Genes Cells 1: 615–632.PubMedCrossRefGoogle Scholar
  7. Takai, Y., Sasaki, T., and Matozaki, 2001, Small GTP-binding proteins, Physiol. Rev. 81: 153–208.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Hiroyuki Nakanishi
    • 1
  • Takuya Sasaki
    • 2
  • Jun Miyoshi
    • 3
  • Yoshimi Takai
    • 1
  1. 1.Department of Molecular Biology and BiochemistryOsaka University Graduate School of Medicine/Faculty of MedicineSuitaJapan
  2. 2.Department of BiochemistryTokushima UniversityJapan
  3. 3.Department of Molecular BiologyOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan

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