Hormone-like peptides in the venoms of marine cone snails.
Hormone-like peptides in the venoms of marine cone snails.
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DOI：
10.1016/j.ygcen.2015.07.012
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发表时间：
2017-04-01
影响因子：
2.7
通讯作者：
Safavi-Hemami H
中科院分区：
文献类型：
--
作者：
Robinson SD;Li Q;Bandyopadhyay PK;Gajewiak J;Yandell M;Papenfuss AT;Purcell AW;Norton RS;Safavi-Hemami H
芋螺属（Conus）的毒液非常复杂，由数百种通常短的富含二硫化物的肽组成，称为芋螺毒素。这些肽具有不同的药理学靶点，注射毒液引起一系列生理反应，包括镇静、麻痹和感觉超负荷。大多数芋螺毒素靶向猎物的神经系统，但毒液肽靶向神经内分泌过程的证据正在出现。例子包括加压素，RFamide神经肽，最近还有胰岛素。为了研究激素/神经肽样分子的多样性，在锥螺毒液中，我们系统地挖掘了几种锥螺的毒腺转录组，并检查了分泌的毒液肽在解剖和注射毒液的澳大利亚锥螺Conus victoriae。使用这种方法，我们鉴定了几种新型激素/神经肽样毒素，包括与蜜蜂脑激素激素原-4类似的肽、软体动物神经节神经肽十一肽和糖蛋白激素家族成员甲状腺刺激素，并证实了胰岛素的存在。我们证实，这些肽中至少有两种不仅在毒腺中表达，而且还形成注射的毒液鸡尾酒的一部分，明确地证明了它们在毒液蛰入中的作用。我们的研究结果表明，激素/神经肽样毒素是芋螺复杂的envenomation策略的多样性和不可分割的一部分。这组毒液成分的探索提供了一个令人兴奋的新途径，发现新的药理学工具和候选药物，补充芋螺毒素。
The venoms of cone snails (genus Conus) are remarkably complex, consisting of hundreds of typically short, disulfide-rich peptides termed conotoxins. These peptides have diverse pharmacological targets, with injection of venom eliciting a range of physiological responses, including sedation, paralysis and sensory overload. Most conotoxins target the prey’s nervous system but evidence of venom peptides targeting neuroendocrine processes is emerging. Examples include vasopressin, RFamide neuropeptides and recently also insulin. To investigate the diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we systematically mined the venom gland transcriptomes of several cone snail species and examined secreted venom peptides in dissected and injected venom of the Australian cone snail Conus victoriae. Using this approach we identified several novel hormone/neuropeptide-like toxins, including peptides similar to the bee brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and thyrostimulin, a member of the glycoprotein hormone family, and confirmed the presence of insulin. We confirmed that at least two of these peptides are not only expressed in the venom gland but also form part of the injected venom cocktail, unambiguously demonstrating their role in envenomation. Our findings suggest that hormone/neuropeptide-like toxins are a diverse and integral part of the complex envenomation strategy of Conus. Exploration of this group of venom components offers an exciting new avenue for the discovery of novel pharmacological tools and drug candidates, complementary to conotoxins.