Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses

At the synapse, presynaptic membranes specialized for vesicular traffic are linked to postsynaptic membranes specialized for signal transduction. The mechanisms that connect pre- and postsynaptic membranes into synaptic junct ions are unknown. Neuroligins and beta-neurexins are neuronal cell-surface proteins that bind to each other and form asymmetric intercellular junction s, To test whether the neuroligin/beta-neurexin junction is related to syna pses, we generated and characterized monoclonal antibodies to neuroligin 1. With these antibodies, we show that neuroligin 1 is synaptic. The neuronal localization, subcellular distribution, and developmental expression of ne uroligin 1 are similar to those of the postsynaptic marker proteins PSD-95 and NMDA-RI receptor. Quantitative immunogold electron microscopy demonstra ted that neuroligin 1 is clustered in synaptic clefts and postsynaptic dens ities. Double immunofluorescence labeling revealed that neuroligin I coloca lizes with glutamatergic but not gamma-aminobutyric acid (GABA)ergic synaps es, Thus neuroligin 1 is a synaptic cell-adhesion molecule that is enriched in postsynaptic densities where it may recruit receptors, channels, and si gnal-transduction molecules to synaptic sites of cell adhesion, In addition , the neuroligin/beta-neurexin junction may be involved in the specificatio n of excitatory synapses.