alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins.
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.
Südhof
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Howard Hughes Medical Institute, Center for Basic Neuroscience, and the Department of Molecular Genetics, The University of Texas Southwestern Medical Center at Dallas, Texas 75390-9111, USA. Thomas.Sudhof@UTSouthwestern.edu
D000818:Animals; D001740:Black Widow Spider; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D018000:Receptors, Peptide / Q000502:physiology*; D013111:Spider Venoms / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D018000:Receptors, Peptide; D013111:Spider Venoms; C034800:alpha-latrotoxin receptor; C020763:alpha-latrotoxin