Proper synaptic adhesion signaling in the control of neural circuit architecture and brain function

Trans-synaptic cell-adhesion molecules are critical for governing various stages of synapse development and specifying neural circuit properties via the formation of multifarious signaling pathways. Recent studies have pinpointed the putative roles of trans-synaptic cell-adhesion molecules in mediating various cognitive functions. Here, we review the literature on the roles of a diverse group of central synaptic organizers, including neurexins (Nrxns), leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs), and their associated binding proteins, in regulating properties of specific type of synapses and neural circuits. In addition, we highlight the findings that aberrant synaptic adhesion signaling leads to alterations in the structures, transmission, and plasticity of specific synapses across diverse brain areas. These results seem to suggest that proper trans-synaptic signaling pathways by Nrxns, LAR-RPTPs, and their interacting network is likely to constitute central molecular complexes that form the basis for cognitive functions, and that these complexes are heterogeneously and complexly disrupted in many neuropsychiatric and neurodevelopmental disorders.