Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming.
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.
Mesh Terms:
Alternative Splicing, Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Fungal Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Neurotransmitter Agents, Presynaptic Terminals, Protein Isoforms, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Synaptic Transmission, Synaptic Vesicles, Two-Hybrid System Techniques, Zinc Fingers, rab3A GTP-Binding Protein
Alternative Splicing, Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins, Fungal Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Neurotransmitter Agents, Presynaptic Terminals, Protein Isoforms, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Synaptic Transmission, Synaptic Vesicles, Two-Hybrid System Techniques, Zinc Fingers, rab3A GTP-Binding Protein
Neuron
Date: Apr. 01, 2001
PubMed ID: 11343654
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