BLACK-WIDOW SPIDER TOXINS - THE PRESENT AND THE FUTURE

The venom of the black widow spider Latrodectus mactans tredisimguttat us was found to contain a family of high molecular weight toxic protei ns inducing a sharp increase in transmitter secretion from the affecte d nerve endings, which are highly specific for vertebrates, or for ins ects, or for crustaceans. Along with the known alpha-latrotoxin, five latroin-sectotoxins affecting the neurotransmitter release from presyn aptic endings of insects and one latrocrustatoxin active only for crus taceans were isolated and studied in detail, alpha-latrotoxin provokes a massive transmitter release from different nerve endings of vertebr ates, whereas other toxins increase the secretion process either in in sects or crustaceans. The cDNAs encoding the putative alpha-latrotoxin and two latroinsectotoxins (alpha-latroinsectotoxin and delta-latroin sectotoxin) precursors were cloned and sequenced. These toxins are pol ypeptides of about 1000 amino acids and share a high level of amino ac id identity. Analysis of amino acid sequences of the three toxins reve als the central regions being almost entirely composed of series of an kyrin-like repeats. Taking into account the size and multifunctional p roperties of latrotoxin its molecule can be divided into several funct ional domains. Immunochemical experiments indicated the presence in th e alpha-latrotoxin molecule of distinguishable functional domains resp onsible for ionophoric and secretogenic actions. The highly purified p reparation of alpha-latrotoxin was shown to contain an additional comp onent, a low molecular weight protein structurally related to crustace an hyperglycemic hormones. Several attempts were made to characterize and isolate alpha-latrotoxin receptor components. The existence of Ca- dependent and Ca-independent binding proteins was found in the presyna ptic membrane preparations. (C) 1998 Elsevier Science Ltd. All rights reserved.