Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

Cell. 2017 Nov 2;171(4):745-769. doi: 10.1016/j.cell.2017.10.024.


Synapses are specialized junctions between neurons in brain that transmit and compute information, thereby connecting neurons into millions of overlapping and interdigitated neural circuits. Here, we posit that the establishment, properties, and dynamics of synapses are governed by a molecular logic that is controlled by diverse trans-synaptic signaling molecules. Neurexins, expressed in thousands of alternatively spliced isoforms, are central components of this dynamic code. Presynaptic neurexins regulate synapse properties via differential binding to multifarious postsynaptic ligands, such as neuroligins, cerebellin/GluD complexes, and latrophilins, thereby shaping the input/output relations of their resident neural circuits. Mutations in genes encoding neurexins and their ligands are associated with diverse neuropsychiatric disorders, especially schizophrenia, autism, and Tourette syndrome. Thus, neurexins nucleate an overall trans-synaptic signaling network that controls synapse properties, which thereby determines the precise responses of synapses to spike patterns in a neuron and circuit and which is vulnerable to impairments in neuropsychiatric disorders.

Publication types

  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • Autistic Disorder / metabolism
  • Autistic Disorder / pathology
  • Cell Adhesion Molecules, Neuronal / chemistry
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Humans
  • Membrane Glycoproteins / metabolism
  • Neural Pathways*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Schizophrenia / metabolism
  • Schizophrenia / pathology
  • Signal Transduction
  • Synapses*
  • Tourette Syndrome / metabolism
  • Tourette Syndrome / pathology


  • Cell Adhesion Molecules, Neuronal
  • Membrane Glycoproteins
  • Protein Isoforms