neuroligin2

Neuroligin-2 (NLGN2) is a member of the neuroligin family of postsynaptic cell-adhesion molecules. It is a single-pass type I membrane protein with an extracellular neuroligin domain that mediates adhesion to presynaptic neurexins and a cytoplasmic tail that interfaces with postsynaptic scaffolding proteins. NLGN2 is strongly expressed at inhibitory synapses in the vertebrate central nervous system and is enriched at GABAergic and glycinergic terminals, where it contributes to the development, maturation, and maintenance of inhibitory synapses. This contrasts with neuroligin-1, which is more associated with excitatory synapses.

Mode of action: Neuroligins bind to presynaptic neurexins in a trans-synaptic complex that promotes presynaptic differentiation and release properties. The intracellular domain of NLGN2 interacts with gephyrin and other scaffolding proteins to cluster GABA receptors at the postsynaptic density, supporting inhibitory synaptic transmission. Neurexin alternative splicing can modulate neuroligin binding, influencing synapse specification and function.

Clinical relevance: Variants in NLGN2 have been implicated in neurodevelopmental and psychiatric disorders, including autism spectrum disorders and schizophrenia, though associations are less common than for some other neuroligins. Mouse models lacking NLGN2 show reductions in inhibitory synaptic transmission and network hyperexcitability, accompanied by behavioral alterations.

See also: neuroligin family, neurexin, gephyrin.