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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 184))

α-Latrotoxin (α-LTX) from black widow spider venom induces exhaustive release of neurotransmitters from vertebrate nerve terminals and endocrine cells. This 130-kDa protein has been employed for many years as a molecular tool to study exocytosis. However, its action is complex: in neurons, α-LTX induces massive secretion both in the presence of extracellular Ca2+ (Ca2+ e) and in its absence; in endocrine cells, it usually requires Ca2+ e. To use this toxin for further dissection of secretory mechanisms, one needs an in-depth understanding of its functions. One such function that explains some α-LTX effects is its ability to form cation-permeable channels in artificial lipid bilayers. The mechanism of α-LTX pore formation, revealed by cryo-electron microscopy, involves toxin assembly into homotetrameric complexes which harbor a central channel and can insert into lipid membranes. However, in biological membranes, α-LTX cannot exert its actions without binding to specific receptors of the plasma membrane. Three proteins with distinct structures have been found to bind α-LTX: neurexin Iα, latrophilin 1, and receptor-like protein tyrosine phosphatase σ. Upon binding a receptor, α-LTX forms channels permeable to cations and small molecules; the toxin may also activate the receptor. To distinguish between the pore- and receptor-mediated effects, and to study structure-function relationships in the toxin, α-LTX mutants have been used.

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Ushkaryov, Y.A., Rohou, A., Sugita, S. (2008). α-Latrotoxin and Its Receptors. In: Südhof, T.C., Starke, K. (eds) Pharmacology of Neurotransmitter Release. Handbook of Experimental Pharmacology, vol 184. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-74805-2_7

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