Abstract
Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / genetics
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Animals
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Animals, Newborn
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Binding Sites
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Blotting, Western
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Calcium-Binding Proteins*
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Cell Adhesion Molecules, Neuronal
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Cell Aggregation / genetics
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Cell Aggregation / physiology
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Cell Communication / physiology
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Cell Differentiation / physiology
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / physiology
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Chickens
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Choline O-Acetyltransferase / chemistry
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Choline O-Acetyltransferase / metabolism
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Female
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Hippocampus / metabolism
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Humans
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Immunomagnetic Separation / methods
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Kidney
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Lipid Bilayers / metabolism
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Membrane Glycoproteins / metabolism
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology
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Mice
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Mutation / physiology
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / immunology
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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PC12 Cells
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Pons / metabolism
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / physiology*
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Proto-Oncogene Proteins c-myc / metabolism
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R-SNARE Proteins
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RNA-Dependent RNA Polymerase / immunology
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RNA-Dependent RNA Polymerase / metabolism
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Rats
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Receptors, AMPA / metabolism
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Recombinant Proteins / chemistry
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Structural Homology, Protein
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Structure-Activity Relationship
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Synapses / genetics
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Synapses / physiology
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Synaptic Vesicles / metabolism
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Synaptotagmins
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Time Factors
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Transfection / methods
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Viral Proteins / immunology
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Viral Proteins / metabolism
Substances
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Calcium-Binding Proteins
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Cell Adhesion Molecules, Neuronal
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Lipid Bilayers
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Membrane Glycoproteins
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Membrane Proteins
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Nerve Tissue Proteins
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Proto-Oncogene Proteins c-myc
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R-SNARE Proteins
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Receptors, AMPA
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Recombinant Proteins
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Viral Proteins
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glutamate receptor ionotropic, AMPA 3
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neuroligin 1
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postsynaptic density proteins
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Synaptotagmins
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neurexin Ibeta
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Choline O-Acetyltransferase
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L protein, vesicular stomatitis virus
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RNA-Dependent RNA Polymerase
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Alanine
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glutamate receptor ionotropic, AMPA 2