The making of neurexins

J Neurochem. 1998 Oct;71(4):1339-47. doi: 10.1046/j.1471-4159.1998.71041339.x.


Neurexins are neuronal cell-surface proteins with up to thousands of isoforms. These isoforms are generated by alternative splicing of transcripts from six promoters in three genes. The structure of neurexins resembles cell-surface receptors with a modular architecture suggestive of a sequential assembly during evolution. Neurexins probably perform multiple functions in the brain. They participate in intercellular junctions in which beta-neurexins tightly bind to a second class of neuronal cell-surface receptors called neuroligins. Intracellularly, the neurexin/neuroligin junction is bound by CASK on the neurexin side and PSD95 on the neuroligin side. CASK and PSD95 are homologous membrane-associated guanylate kinases that bind to the neurexin/neuroligin junction via PDZ domains, creating an asymmetric junction (neurexin/neuroligin) with similar intracellular binding partners. In addition to a function as cell-adhesion molecules, neurexins may also serve as a signalling receptor, because a class of ligands for alpha-neurexins called neurexophilins is similar to peptide hormones. Finally, at least one neurexin isoform, neurexin Ialpha, represents a high-affinity receptor for alpha-latrotoxin, which is a potent excitatory neurotoxin. Thus, neurexins constitute a large family of neuronal receptors that may be involved in multiple interactive functions between neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Glycoproteins
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neuropeptides
  • Sequence Homology, Amino Acid


  • Glycoproteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • neurexin II
  • neurexin IIIalpha
  • neurexophilin