Abstract
Neurexins are neuronal cell surface proteins with hundreds of isoforms generated by alternative splicing. Here we describe neuroligin 1, a neuronal cell surface protein that is enriched in synaptic plasma membranes and acts as a splice site-specific ligand for beta-neurexins. Neuroligin 1 binds to beta-neurexins only if they lack an insert in the alternatively spliced sequence of the G domain, but not if they contain an insert. The extracellular sequence of neuroligin 1 is composed of a catalytically inactive esterase domain homologous to acetylcholinesterase. In situ hybridization reveals that alternative splicing of neurexins at the site recognized by neuroligin 1 is highly regulated. These findings support a model whereby alternative splicing of neurexins creates a family of cell surface receptors that confers interactive specificity onto their resident neurons.
Publication types
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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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Alternative Splicing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Brain / cytology
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Brain / metabolism*
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Brain Chemistry
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Cell Adhesion Molecules, Neuronal
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Cell Membrane / chemistry
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Esterases / genetics
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Hippocampus / cytology
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Hippocampus / metabolism
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Ligands
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / isolation & purification
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism*
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Protein Binding
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Rats
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Recombinant Proteins / metabolism
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Sequence Analysis
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Sequence Homology, Amino Acid
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Synapses / chemistry
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Tissue Distribution
Substances
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Cell Adhesion Molecules, Neuronal
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Ligands
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Membrane Proteins
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Nerve Tissue Proteins
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Recombinant Proteins
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neuroligin 1
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neurexin Ibeta
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Esterases