Previous studies suggested that postsynaptic neuroligins form a trans-synaptic complex with presynaptic beta-neurexins, but not with presynaptic alpha-neurexins. Unexpectedly, we now find that neuroligins also bind alpha-neurexins and that alpha- and beta-neurexin binding by neuroligin 1 is regulated by alternative splicing of neuroligin 1 (at splice site B) and of neurexins (at splice site 4). In neuroligin 1, splice site B is a master switch that determines alpha-neurexin binding but leaves beta-neurexin binding largely unaffected, whereas alternative splicing of neurexins modulates neuroligin binding. Moreover, neuroligin 1 splice variants with distinct neurexin binding properties differentially regulate synaptogenesis: neuroligin 1 that binds only beta-neurexins potently stimulates synapse formation, whereas neuroligin 1 that binds to both alpha- and beta-neurexins more effectively promotes synapse expansion. These findings suggest that neuroligin binding to alpha- and beta-neurexins mediates trans-synaptic cell adhesion but has distinct effects on synapse formation, indicating that expression of different neuroligin and neurexin isoforms specifies a trans-synaptic signaling code.
Pubmed ID: 16242404 RIS Download
Mesh terms: Alternative Splicing | Animals | Animals, Newborn | Blotting, Western | Cell Adhesion | Cell Adhesion Molecules, Neuronal | Cells, Cultured | Chromatography, Affinity | Electrophoretic Mobility Shift Assay | Glycoproteins | Green Fluorescent Proteins | Hippocampus | Humans | Immunohistochemistry | Membrane Proteins | Microtubule-Associated Proteins | Mutagenesis | Nerve Tissue Proteins | Neurons | Neuropeptides | Protein Binding | Rats | Recombinant Proteins | Synapses | Synapsins | Transfection
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