PMID:9430716

Citation	Geppert, M, Khvotchev, M, Krasnoperov, V, Goda, Y, Missler, M, Hammer, RE, Ichtchenko, K, Petrenko, AG and Südhof, TC (1998) Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action. J. Biol. Chem. 273:1705-10
Abstract	alpha-Latrotoxin is a potent neurotoxin from black widow spider venom that binds to presynaptic receptors and causes massive neurotransmitter release. A surprising finding was the biochemical description of two distinct cell surface proteins that bind alpha-latrotoxin with nanomolar affinities; Neurexin I alpha binds alpha-latrotoxin in a Ca(2+)-dependent manner, and CIRL/latrophilin binds in a Ca(2+)-independent manner. We have now generated and analyzed mice that lack neurexin I alpha to test its importance in alpha-latrotoxin action. alpha-Latrotoxin binding to brain membranes from mutant mice was decreased by almost 50% compared with wild type membranes; the decrease was almost entirely due to a loss of Ca(2+)-dependent alpha-latrotoxin binding sites. In cultured hippocampal neurons, alpha-latrotoxin was still capable of activating neurotransmission in the absence of neurexin I alpha. Direct measurements of [3H]glutamate release from synaptosomes, however, showed a major decrease in the amount of release triggered by alpha-latrotoxin in the presence of Ca2+. Thus neurexin I alpha is not essential for alpha-latrotoxin action but contributes to alpha-latrotoxin action when Ca2+ is present. Viewed as a whole, our results show that mice contain two distinct types of alpha-latrotoxin receptors with similar affinities and abundance but different properties and functions. The action of alpha-latrotoxin may therefore be mediated by independent parallel pathways, of which the CIRL/latrophilin pathway is sufficient for neurotransmitter release, whereas the neurexin I alpha pathway contributes to the Ca(2+)-dependent action of alpha-latrotoxin.
Links	PubMed
Keywords	Alternative Splicing; Animals; Brain/metabolism; Calcium/metabolism; Cell Membrane/metabolism; Chromosome Mapping; Glutamic Acid/metabolism; Glycoproteins; Mice; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neuropeptides; Receptors, Peptide/genetics; Receptors, Peptide/metabolism; Spider Venoms/genetics; Spider Venoms/metabolism; Synaptic Transmission; Synaptosomes/metabolism
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.