Südhof T C
Howard Hughes Medical Institute, Center for Basic Neuroscience, and the Department of Molecular Genetics, The University of Texas Southwestern Medical Center at Dallas, Texas 75390-9111, USA.
Annu Rev Neurosci. 2001;24:933-62. doi: 10.1146/annurev.neuro.24.1.933.
alpha-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. alpha-Latrotoxin is a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating exocytosis, alpha-latrotoxin binds to two distinct families of neuronal cell-surface receptors, neurexins and CLs (Cirl/latrophilins), which probably have a physiological function in synaptic cell adhesion. Binding of alpha-latrotoxin to these receptors does not in itself trigger exocytosis but serves to recruit the toxin to the synapse. Receptor-bound alpha-latrotoxin then inserts into the presynaptic plasma membrane to stimulate exocytosis by two distinct transmitter-specific mechanisms. Exocytosis of classical neurotransmitters (glutamate, GABA, acetylcholine) is induced in a calcium-independent manner by a direct intracellular action of alpha-latrotoxin, while exocytosis of catecholamines requires extracellular calcium. Elucidation of precisely how alpha-latrotoxin works is likely to provide major insight into how synaptic vesicle exocytosis is regulated, and how the release machineries of classical and catecholaminergic neurotransmitters differ.
α- Latrotoxin是一种源自黑寡妇蜘蛛毒液的强效神经毒素，可触发突触前神经末梢的突触小泡胞吐作用。α- Latrotoxin是一种大型蛋白质毒素（120 kDa），含有22个锚蛋白重复序列。在刺激胞吐作用时，α- Latrotoxin与两类不同的神经元细胞表面受体结合，即神经配素和CLs（Cirl/促毒亲和素），它们可能在突触细胞黏附中具有生理功能。α- Latrotoxin与这些受体的结合本身并不会触发胞吐作用，而是将毒素募集到突触。与受体结合的α- Latrotoxin随后插入突触前质膜，通过两种不同的递质特异性机制刺激胞吐作用。经典神经递质（谷氨酸、γ-氨基丁酸、乙酰胆碱）的胞吐作用是由α- Latrotoxin的直接细胞内作用以钙非依赖性方式诱导的，而儿茶酚胺的胞吐作用则需要细胞外钙。精确阐明α- Latrotoxin的作用机制可能会为突触小泡胞吐作用的调节方式以及经典和儿茶酚胺能神经递质的释放机制如何不同提供重要见解。
