Orchestrating synaptic strength by neuroligin-confined nanoscale organization

The synaptic nanocluster refers to the nanoscale accumulation of synaptic proteins that ensures the fidelity of synaptic transmission. These nanoclusters align pre- and post-synaptic machineries across the synaptic cleft, enabling neurotransmitter release to occur precisely opposite postsynaptic receptors. In vertebrates, neuroligins are key postsynaptic cell adhesion molecules that help maintain synaptic function. Recent superresolution microscopy studies have shown that neuroligins themselves form nanoclusters and regulate the nanoscale distribution of synaptic proteins, suggesting a role in orchestrating synaptic strength through nanocluster organization. In this review, we summarize recent advances in understanding how neuroligin subtype specificity influences the organization of postsynaptic receptors and how neuroligin-ligand interactions modulate nanoscale architecture. We also discuss how disruption in those nanoclusters can disturb synaptic strength.