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-neurexin binding was essential for the ability of
postsynaptic neuroligin-1 to dramatically increase
synapse density, suggesting a neurexin-independent mechanism of
synapse formation. Moreover, neuroligin-1 dimerization was not required for either the non-neuronal or the
neuronal synapse-formation
assay. Nevertheless, both alpha-neurexin binding and neuroligin-1 dimerization were essential for the increase in apparent
synapse size that is induced by neuroligin-1 in transfected
neurons. Thus, neuroligin-1 performs diverse synaptic functions by mechanisms that include as essential components of alpha-neurexin binding and
neuroligin dimerization, but extend beyond these activities.
