biostudies-literatureKo JNIMH NIH HHS3244-55https://www.ebi.ac.uk/biostudies/studies/S-EPMC2771087biostudies-literatureUnknown28(20)Postsynaptic neuroligins are thought to perform essential functions in synapse validation and synaptic transmission by binding to, and dimerizing, presynaptic alpha- and beta-neurexins. To test this hypothesis, we examined the functional effects of neuroligin-1 mutations that impair only alpha-neurexin binding, block both alpha- and beta-neurexin binding, or abolish neuroligin-1 dimerization. Abolishing alpha-neurexin binding abrogated neuroligin-induced generation of neuronal synapses onto transfected non-neuronal cells in the so-called artificial synapse-formation assay, even though beta-neurexin binding was retained. Thus, in this assay, neuroligin-1 induces apparent synapse formation by binding to presynaptic alpha-neurexins. In transfected neurons, however, neither alpha- nor beta-neuThe EMBO journalNeuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation.PMC2771087R37 MH052804Boucard AAArac DSudhof TCZhang CKo JBrunger ATfalseNeuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation.Postsynaptic neuroligins are thought to perform essential functions in synapse validation and synaptic transmission by binding to, and dimerizing, presynaptic alpha- and beta-neurexins. To test this hypothesis, we examined the functional effects of neuroligin-1 mutations that impair only alpha-neurexin binding, block both alpha- and beta-neurexin binding, or abolish neuroligin-1 dimerization. Abolishing alpha-neurexin binding abrogated neuroligin-induced generation of neuronal synapses onto transfected non-neuronal cells in the so-called artificial synapse-formation assay, even though beta-neurexin binding was retained. Thus, in this assay, neuroligin-1 induces apparent synapse formation by binding to presynaptic alpha-neurexins. In transfected neurons, however, neither alpha- nor beta-neu2009-01-01T00:00:00Z2009 Oct2026-03-16T16:56:07.248Z2025-09-01T03:06:25.586ZS-EPMC27710871973041110.1038/emboj.2009.249