RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses

eLife

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[1] DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany;Freie Universität Berlin, Institut für Biologie, Berlin, Germany;Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany;NeuroCure Cluster of Excellence, Berlin, Germany;Freie Universität Berlin, Institut für Biologie, Berlin, Germany;NeuroCure Cluster of Excellence, Berlin, Germany;DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany;Institut für Neurophysiologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;Institut für Neurophysiologie, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;NeuroCure Cluster of Excellence, Berlin, Germany;Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany;NeuroCure Cluster of Excellence, Berlin, Germany;NeuroCure Cluster of Excellence, Berlin, Germany;DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany;Neuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;Neuroscience Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;

关键词: neurotransmitter release;    active zone;    vesicle priming;    calcium channel;    hippocampus;    Mouse;   

DOI  :  10.7554/eLife.43243

来源: publisher

【 摘 要 】

10.7554/eLife.43243.001All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in neurotransmitter release at different central murine synapses and thus contributes to synaptic diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active zone. We suggest that differences in the active zone organization may dictate the role a protein plays in synaptic transmission and that differences in active zone architecture is a major determinant factor in the functional diversity of synapses.

【 授权许可】

CC BY