Figure 7.

Trans-synaptic neurexin-neuroligin complexes shape excitatory and inhibitory synapses. Presynaptic α-neurexins or β-neurexins (red) can interact with dimeric neuroligins (green) across the synaptic cleft to regulate important aspects of establishment, differentiation and maturation of synapses. Isoforms and splice variants of both molecules have been proposed to be differentially distributed at excitatory or inhibitory synapses to establish specificity. Note that presence of β-neurexins (β-Nrxn) at inhibitory terminals is unclear, while for neuroligins (Nlgn), Nlgn2 and Nlgn4 show quite specific localization and roles at inhibitory synapses. Intracellularly, the cytosolic domains of Nrxn and Nlgn are able to cluster components of the presynaptic release machinery and of postsynaptic signaling pathways and transmitter receptors (R). The clustering ability of Nrxn and Nlgn variants at excitatory or inhibitory synapses is mostly derived from cell culture assays. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; GABA, γ-aminobutyric acid; NMDAR, N-methyl-D-aspartate receptor; PSD95, postsynaptic density protein-95; VGat, vesicular GABA transporter; VGlu, vesicular glutamate transporter.