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

Abstract

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-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

An option space for early neural evolution

“…During predation, several animals use special glands to catch or kill prey. These include the nematocyst and toxin-producing gland cells of cnidarians [39,40], the colloblasts of ctenophores [41] or the slime glands of onychophorans [42]. These structures are under nervous control [41,43] and sensory stimuli regulate secretion or discharge.…”

“…These structures are under nervous control [41,43] and sensory stimuli regulate secretion or discharge. For example, in cnidarians, toxin-gland and cnidocyte discharge are triggered by prey encounter [40], and are also influenced by light [44] (IO systems). In small interstitial marine invertebrates, gland systems often contribute to locomotion by regulating surface adhesion, stopping, turning or ciliary gliding.…”

BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker

“…They contain a variety of toxic proteins and peptides, including potent toxins affecting the transient receptor protein vanilloid (TRPV1), acid-sensing ion channels, voltage-gated Na + (Na V ) and K + channels, as well as secondary metabolites [4]. Recently, the ectodermal gland cells were also reported as a toxin production compartment in sea anemones [5]. Characterized peptide toxins from sea anemones can affect ion channels either by blocking the current or modifying the gating mechanism.…”

Evolution and diversification of the cnidarian venom system

“…For example, C. fleckeri has a relatively large body and a higher ratio of mastigophores (the longest of the penetrant cnidae) correlating to the large organisms which they prey upon [41]. In addition to cnidae, venom of Cnidarians was shown to be also synthesized in other cell types such as ectodermal and endodermal gland cells and other, still unknown, cell types [42,43]. [90,91].…”

“…Toxicity assays on blowfly and 3-days-old zebrafish larvae were performed as described before [42,164]. The zebrafish larvae were kindly provided by Dr Y Gothilf (Tel Aviv University).…”