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Negative regulation of exocytosis at the nerve terminal

Molecular Psychiatry volume 7, pages 536–537 (2002)Cite this article

SIR – Neurons communicate with each other through synaptic connections, and short-term and long-term plasticity of synaptic transmission is believed to be an important cellular basis of learning and memory. Synaptic transmission is conducted by neurotransmitters released from presynaptic nerve terminals by exocytosis of synaptic vesicle contents. Various protein kinases as well as a lipid kinase such as PI-3 kinase have been shown to enhance neurotransmitter release in various neuronal preparations. Generally, all regulatory systems have a set of both positive and negative regulators. For example, we can drive a car safely by controlling the accelerator and the brake properly. However, no protein kinases involved in negative regulation have been reported so far. Recently, we found that two types of non-receptor protein tyrosine kinases are negative regulators of neurotransmitter release.1,2,3

Src family kinases (SFK) are non-receptor tyrosine kinases and 10 different members have been identified so far.4 Among these, Src is accumulated in synaptic vesicles and accounts for the majority of synaptic vesicle tyrosine kinase activity, however, its functional roles have not been clarified. We found that pretreating cells with SFK inhibitors extensively enhanced Ca2+-dependent dopamine (DA) release from clonal rat pheochromocytoma PC12 cells.3 PC12 cells release DA by Ca2+-dependent exocytosis of secretory vesicle contents. Transient expression of constitutively active v-Src suppressed Ca2+-dependent exocytosis in an activity-dependent manner. DA release induced by Ca2+ ionophore was also affected by these treatments, indicating that certain steps downstream from Ca2+ entry are regulated by tyrosine phosphorylation. Ca2+-induced glutamate release from cultured rat cerebellar granule cells is also enhanced by treatment with SFK inhibitors, indicating that Src regulates presynaptic function negatively in central neurons.

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Authors and Affiliations

  1. Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo, Japan

    M Takahashi

  2. Institute for Molecular and Cellular Regulation, Gunma University, Showa-machi, Maebashi, Gunma, Japan

    H Ohnishi

Authors
  1. M Takahashi
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  2. H Ohnishi
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Correspondence to M Takahashi.

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Takahashi, M., Ohnishi, H. Negative regulation of exocytosis at the nerve terminal. Mol Psychiatry 7, 536–537 (2002). https://doi.org/10.1038/sj.mp.4001050

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