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α-Latrotoxin and Its Receptors

  • Chapter
Pharmacology of Neurotransmitter Release

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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Authors and Affiliations

  1. Division of Cell and Molecular Biology, Imperial College London, London, SW7 2AY, UK

    Yuri A. Ushkaryov & Alexis Rohou

  2. Division of Cellular and Molecular Biology, Toronto Western Research Institute, Toronto, Ontario, M5T 2S8, Canada

    Shuzo Sugita

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  1. Yuri A. Ushkaryov
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  3. Shuzo Sugita
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  1. Howard Hughes Medical Institute and Center for Basic Neuroscience, UT Southwestern Medical Center, 6000 Harry Hines Blvd. NA4.118, Dallas, TX 75390, USA

    Thomas C. Südhof

  2. Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, D-79104 Freiburg i.Br., Germany

    K. Starke  & Klaus Starke  & 

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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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