Neurexins are functional alpha-latrotoxin receptors

Neuron. 1999 Mar;22(3):489-96. doi: 10.1016/s0896-6273(00)80704-7.


Alpha-latrotoxin is a potent neurotoxin that triggers synaptic exocytosis. Surprisingly, two distinct neuronal receptors for alpha-latrotoxin have been described: CIRL/latrophilin 1 (CL1) and neurexin-1alpha. Alpha-latrotoxin is thought to trigger exocytosis by binding to CL1, while the role of neurexin 1alpha is uncertain. Using PC12 cells, we now demonstrate that neurexins indeed function as alpha-latrotoxin receptors that are at least as potent as CL1. Both alpha- and beta-neurexins represent autonomous alpha-latrotoxin receptors that are regulated by alternative splicing. Similar to CL1, truncated neurexins without intracellular sequences are fully active; therefore, neurexins and CL1 recruit alpha-latrotoxin but are not themselves involved in exocytosis. Thus, alpha-latrotoxin is unique among neurotoxins, because it utilizes two unrelated receptors, probably to amplify recruitment of alpha-latrotoxin to active sites.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Animals
  • Binding Sites
  • Calcium / physiology
  • Exocytosis / physiology
  • Glycoproteins
  • Immunoglobulin G / genetics
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neuropeptides
  • PC12 Cells
  • Rats
  • Receptors, Peptide / biosynthesis
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Receptors, Peptide / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spider Venoms / metabolism*
  • Transfection


  • Glycoproteins
  • Immunoglobulin G
  • Nerve Tissue Proteins
  • Neuropeptides
  • Receptors, Peptide
  • Recombinant Fusion Proteins
  • Spider Venoms
  • alpha-latrotoxin receptor
  • neurexophilin
  • neurexin Ibeta
  • alpha-latrotoxin
  • Calcium