Abstract
Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing / genetics
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Animals
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Binding Sites / genetics
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism
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Neurotransmitter Agents / metabolism*
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Presynaptic Terminals / metabolism*
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary / genetics
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Sequence Homology, Amino Acid
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Synaptic Transmission / physiology*
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Synaptic Vesicles / metabolism*
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Two-Hybrid System Techniques
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Zinc Fingers / physiology
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rab3A GTP-Binding Protein / metabolism
Substances
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DNA-Binding Proteins
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Fungal Proteins
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Nerve Tissue Proteins
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Neurotransmitter Agents
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Protein Isoforms
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Unc13a protein, rat
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rab3A GTP-Binding Protein