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Spider farming, spider venom and neurexins
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neurex r s Spiders make many people shudder. Nevertheless, research into spider venoms is now burgeoning, one of the reasons being that the constituent proteins and peptides of spider venom are useful pharmacological tools. One species that has attracted much attention is the black widow spider (Lactrodecms mactans). Female black widows are notorious for killing the male after mating. Their venom acts on human nerve synapses, causing a massive release of neurotransmitter and blocking its reuptake. Peripheral nerves lose the ability to stimulate muscle contractio'.~ after an initial phase of muscular rigidity, and the victim dies from asphyxia. The principal active component of the venom is t~-latrotoxin, which Yuri Ushkaryov, now in the Department of Biochemistry, Imperial College, London, UK, began to study while researching in Moscow. To obtain just 5 g of material 25 000 female spiders were needed and workers had to comb Central Asia to find them. The effects of ~-latrotoxin are highly specific to nerve cells and it affects a wide variety of neurons. The hunt for a receptor 0:.~atbound ~e toxin and was present on many types of neurons led to the disco,,ery of a family of neuron-specific proteins called neurexins. These are ce~.i-surface receptors consisting of a large glycosylated extrace!lular domain, a sing!e transmembrane region and a short intracellular domain {see model on right). Perhaps the most exciting discovery was that neurexins exist in a large variety of alternatively spliced forms. Ushkaryov is now looking at the detailed structure of the receptor, the intracellular proteins with which the neurexins interact and the function of the neurexin--~-latrotoxin complex. A full understanding of these has implications for the ©1996, ELsevierScience Ltd 1357 - 4310/96/515.06
action of neural networks which, in the words of Dr Ushkaryov, '...in terms of complexity make even the most elaborate spiders ~ webs look trivial'. Although muc~ of the research into spider venoms has concentrated L on the black widow and tunnel web varieties, tarantulas {Grammostola spatulataI are the special interest of Brian Whitely. who has started his own company, (Invertebrate Biologics, CA, USAI to harvest their venom. Whitely, a biochemist, had been interested in spiders as a hobby for many years and increasingly realized how useful their venoms were as research tools. Tarantulas are interesting because their venom contains large quantities of protein virtually devoid of protease activity: this makes them relatively clean research tools. Although generally regarded as harmless to healthy adults, tarantula venom does contain peptides that exhibit activity in vertebrates. Whitely is now an expert on tarantulas and offers venom from 12 different species. These venoms are being used by researchers to help them develop new drugs and insecticides by screening for speciesspecific agents, ion-channel-blocking activity and a variety of novel biological activities, limited only by the innovative capacity of the screen. Whitely taught himself how to extract the spiders'
venom using electrical stimulation after lightly anaesthetizing them using CO2; nothing stronger can be used they have to be fully active for the venom to be extracted. According to Dr Whitely, 'The trick is to handle them with a finn grip after they come to. It is surprisingly easy once you get the hang of it but, in the case of really large ones, you sometimes wonder who is in control.' As a result of these techniques we may eventually understand more about the control of the nervous system and how to control ardu'opod-mediated disease. David B. Jack 1
O
neurex r s Spiders make many people shudder. Nevertheless, research into spider venoms is now burgeoning, one of the reasons being that the constituent proteins and peptides of spider venom are useful pharmacological tools. One species that has attracted much attention is the black widow spider (Lactrodecms mactans). Female black widows are notorious for killing the male after mating. Their venom acts on human nerve synapses, causing a massive release of neurotransmitter and blocking its reuptake. Peripheral nerves lose the ability to stimulate muscle contractio'.~ after an initial phase of muscular rigidity, and the victim dies from asphyxia. The principal active component of the venom is t~-latrotoxin, which Yuri Ushkaryov, now in the Department of Biochemistry, Imperial College, London, UK, began to study while researching in Moscow. To obtain just 5 g of material 25 000 female spiders were needed and workers had to comb Central Asia to find them. The effects of ~-latrotoxin are highly specific to nerve cells and it affects a wide variety of neurons. The hunt for a receptor 0:.~atbound ~e toxin and was present on many types of neurons led to the disco,,ery of a family of neuron-specific proteins called neurexins. These are ce~.i-surface receptors consisting of a large glycosylated extrace!lular domain, a sing!e transmembrane region and a short intracellular domain {see model on right). Perhaps the most exciting discovery was that neurexins exist in a large variety of alternatively spliced forms. Ushkaryov is now looking at the detailed structure of the receptor, the intracellular proteins with which the neurexins interact and the function of the neurexin--~-latrotoxin complex. A full understanding of these has implications for the ©1996, ELsevierScience Ltd 1357 - 4310/96/515.06
action of neural networks which, in the words of Dr Ushkaryov, '...in terms of complexity make even the most elaborate spiders ~ webs look trivial'. Although muc~ of the research into spider venoms has concentrated L on the black widow and tunnel web varieties, tarantulas {Grammostola spatulataI are the special interest of Brian Whitely. who has started his own company, (Invertebrate Biologics, CA, USAI to harvest their venom. Whitely, a biochemist, had been interested in spiders as a hobby for many years and increasingly realized how useful their venoms were as research tools. Tarantulas are interesting because their venom contains large quantities of protein virtually devoid of protease activity: this makes them relatively clean research tools. Although generally regarded as harmless to healthy adults, tarantula venom does contain peptides that exhibit activity in vertebrates. Whitely is now an expert on tarantulas and offers venom from 12 different species. These venoms are being used by researchers to help them develop new drugs and insecticides by screening for speciesspecific agents, ion-channel-blocking activity and a variety of novel biological activities, limited only by the innovative capacity of the screen. Whitely taught himself how to extract the spiders'
venom using electrical stimulation after lightly anaesthetizing them using CO2; nothing stronger can be used they have to be fully active for the venom to be extracted. According to Dr Whitely, 'The trick is to handle them with a finn grip after they come to. It is surprisingly easy once you get the hang of it but, in the case of really large ones, you sometimes wonder who is in control.' As a result of these techniques we may eventually understand more about the control of the nervous system and how to control ardu'opod-mediated disease. David B. Jack 1