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Roles of Tomosyn in Neurotransmitter Release

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Presynaptic Terminals

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Abstract

SNARE complexes and synaptotagmin mediate synaptic vesicle fusion with the plasma membrane of the active zone for the neurotransmitter release from presynaptic nerve terminals responding to neuronal signals. Many regulatory proteins for the SNARE complex formation have been identified. Among them, our originally identified protein, tomosyn, is likely to be a key molecule for the regulation of the SNARE complex-involved pre-fusion step and the Ca2+-triggered synaptic vesicle fusion step. Tomosyn inhibits SNARE complex formation and thereby inhibits synaptic vesicle fusion by sequestering target SNAREs through its C-terminal VAMP-like domain in a Ca2+-independent manner. The N-terminal WD40 repeats are the site for its binding to synaptotagmin-1, a Ca2+-sensor protein, in a Ca2+-dependent manner. The interaction negatively regulates the Ca2+-dependent synaptic vesicle fusion mediated by synaptotagmin-1. Thus, tomosyn is a potent inhibitor, temporally and stepwisely regulating the synaptic vesicle fusion at the active zone, for the synchronized and fast neurotransmitter release.

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Authors and Affiliations

  1. Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    Yasunori Yamamoto & Toshiaki Sakisaka

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  1. Yasunori Yamamoto
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  2. Toshiaki Sakisaka
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Correspondence to Toshiaki Sakisaka .

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  1. Department of Physiology, Tokyo Medical University, Tokyo, Japan

    Sumiko Mochida

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Yamamoto, Y., Sakisaka, T. (2015). Roles of Tomosyn in Neurotransmitter Release. In: Mochida, S. (eds) Presynaptic Terminals. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55166-9_5

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