Pharmacology of Neurotransmitter Release pp 171-206

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

α-Latrotoxin and Its Receptors

  • Yuri A. Ushkaryov
  • Alexis Rohou
  • Shuzo Sugita

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Yuri A. Ushkaryov
    • 1
  • Alexis Rohou
    • 1
  • Shuzo Sugita
    • 2
  1. 1.Division of Cell and Molecular BiologyImperial College LondonLondonUK
  2. 2.Division of Cellular and Molecular BiologyToronto Western Research InstituteToronto, OntarioCanada

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