alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins

Annu Rev Neurosci. 2001;24:933-62. doi: 10.1146/annurev.neuro.24.1.933.

Abstract

alpha-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. alpha-Latrotoxin is a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating exocytosis, alpha-latrotoxin binds to two distinct families of neuronal cell-surface receptors, neurexins and CLs (Cirl/latrophilins), which probably have a physiological function in synaptic cell adhesion. Binding of alpha-latrotoxin to these receptors does not in itself trigger exocytosis but serves to recruit the toxin to the synapse. Receptor-bound alpha-latrotoxin then inserts into the presynaptic plasma membrane to stimulate exocytosis by two distinct transmitter-specific mechanisms. Exocytosis of classical neurotransmitters (glutamate, GABA, acetylcholine) is induced in a calcium-independent manner by a direct intracellular action of alpha-latrotoxin, while exocytosis of catecholamines requires extracellular calcium. Elucidation of precisely how alpha-latrotoxin works is likely to provide major insight into how synaptic vesicle exocytosis is regulated, and how the release machineries of classical and catecholaminergic neurotransmitters differ.

Publication types

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

MeSH terms

  • Animals
  • Black Widow Spider
  • Humans
  • Nerve Tissue Proteins / physiology*
  • Neurotransmitter Agents / physiology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Receptors, Peptide / physiology*
  • Spider Venoms / toxicity*
  • Synapses / drug effects
  • Synapses / physiology*

Substances

  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Receptors, Peptide
  • Spider Venoms
  • alpha-latrotoxin receptor
  • alpha-latrotoxin