Silva John-Paul, Suckling Jason, Ushkaryov Yuri
Division of Cell and Molecular Biology, Imperial College London, Exhibition Road, London, UK.
J Neurochem. 2009 Oct;111(2):275-90. doi: 10.1111/j.1471-4159.2009.06329.x. Epub 2009 Aug 13.
For more than three decades, the venom of the black widow spider and its principal active components, latrotoxins, have been used to induce release of neurotransmitters and hormones and to study the mechanisms of exocytosis. Given the complex nature of alpha--latrotoxin (alpha-LTX) actions, this research has been continuously overshadowed by many enigmas, misconceptions and perpetual changes of the underlying hypotheses. Some of the toxin's mechanisms of action are still not completely understood. Despite all these difficulties, the extensive work of several generations of neurobiologists has brought about a great deal of fascinating insights into pre-synaptic processes and has led to the discovery of several novel proteins and synaptic systems. For example, alpha-LTX studies have contributed to the widespread acceptance of the vesicular theory of transmitter release. Pre-synaptic receptors for alpha-LTX--neurexins, latrophilins and protein tyrosine phosphatase sigma--and their endogenous ligands have now become centrepieces of their own areas of research, with a potential of uncovering new mechanisms of synapse formation and regulation that may have medical implications. However, any future success of alpha-LTX research will require a better understanding of this unusual natural tool and a more precise dissection of its multiple mechanisms.
三十多年来，黑寡妇蜘蛛的毒液及其主要活性成分——Latrotoxins毒素，一直被用于诱导神经递质和激素的释放，并用于研究胞吐作用的机制。鉴于α-Latrotoxin（α-LTX）作用的复杂性，这项研究一直被许多谜团、误解以及潜在假设的不断变化所笼罩。该毒素的一些作用机制仍未完全被理解。尽管存在所有这些困难，几代神经生物学家的广泛研究工作已对突触前过程带来了许多引人入胜的见解，并导致发现了几种新的蛋白质和突触系统。例如，α-LTX研究有助于递质释放的囊泡理论被广泛接受。α-LTX的突触前受体——神经连接蛋白、亲嗜性毒素受体和蛋白酪氨酸磷酸酶σ——及其内源性配体，现在已成为各自研究领域的核心，有可能揭示出可能具有医学意义的突触形成和调节的新机制。然而，α-LTX研究未来的任何成功都需要更好地理解这种独特的天然工具，并更精确地剖析其多种机制。
