Neurexins: molecular codes for shaping neuronal synapses

The function of neuronal circuits relies on the properties of individual neuronal cells and their synapses. We propose that a substantial degree of synapse formation and function is instructed by molecular codes resulting from transcriptional programmes. Recent studies on the Neurexin protein family and its ligands provide fundamental insight into how synapses are assembled and remodelled, how synaptic properties are specified and how single gene mutations associated with neurodevelopmental and psychiatric disorders might modify the operation of neuronal circuits and behaviour. In this Review, we first summarize insights into Neurexin function obtained from various model organisms. We then discuss the mechanisms and logic of the cell type-specific regulation of Neurexin isoforms, in particular at the level of alternative mRNA splicing. Finally, we propose a conceptual framework for how combinations of synaptic protein isoforms act as 'senders' and 'readers' to instruct synapse formation and the acquisition of cell type-specific and synapse-specific functional properties.

Automated summary

Studies have shown that synapse formation and function are guided by molecular codes resulting from transcriptional programmes. Insight from the Neurexin protein family and its ligands sheds light on synaptic assembly, properties, and the impact of single gene mutations on neuronal circuits and behavior. Cell type-specific regulation of Neurexin isoforms, particularly at the level of alternative mRNA splicing, plays a crucial role in instructing synapse formation and functional properties.