Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones

Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretionmechanismis an ancestral evolutionary state of the venom deliverymachinery in sea anemones.

水母、水螅、珊瑚和海葵（刺胞动物门）以其有毒的刺细胞（刺丝囊细胞）而闻名，这些细胞用于捕食和防御。然而，我们在此表明，海葵（星状海葵）的强效I型神经毒素Nv1局限于外胚层腺细胞而非刺丝囊细胞。我们证明在遇到甲壳类猎物时会大量分泌Nv1。刺丝囊的伴随释放可能会刺穿猎物，加速毒素渗透。通过将重组Nv1应用于鱼或甲壳类幼虫的生存环境中，它们会迅速麻痹，这进一步证明了毒素在海水中的效力。对其他海葵物种的分析显示，在优美侧花海葵中，I型神经毒素也出现在腺细胞中，而在常见物种绿海葵中，I型毒素既存在于刺丝囊细胞中，也存在于外胚层腺细胞中。基于刺丝囊细胞和基于腺细胞的毒液注入机制可能反映了海葵物种在生态和摄食习性上的重大差异。总体而言，神经毒素在腺细胞中的免疫定位改变了文献中普遍认为的海葵神经毒素仅由带刺的刺丝囊细胞产生和释放的观点，并提出这种毒素分泌机制可能是海葵毒液释放机制的一种原始进化状态的可能性。