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Calitoxin, also known as CLX, is a sea anemone toxin which increases neurotransmitter release at invertebrate neuromuscular junctions. Two different toxins, namely CLX-1 and CLX-2, can be distinguished. It targets crabs and octopuses, among other invertebrates.

Discovery

Calitoxin (CLX) was isolated by a team of Italian researchers in Naples. The name derives from the organism the toxin was isolated from: the sea anemone Calliactis parasitica. The team isolated and sequenced the polypeptide chain. They also published details on the toxins effects in vitro on crustacean tissue preparations, including nerve and muscle. Their findings were published in the journal Biochemistry in 1989.

Sources

Calitoxin is a highly potent neurotoxin. It is produced by the sea anemone Calliactis parasitica and stored in the nematocysts of stinging cells (cnidocytes). This sea anemone is a species from the Hormathiidae family and is present along the European coasts of the Atlantic Ocean and in the Mediterranean Sea.

Structure and chemistry

The formula for calitoxin is C₂₀₃H₃₀₅N₅₅O₇₂S₇. It has a molecular mass of mass of 4886 Daltons. It has an isoelectric point at pH 5.4. The amino acid sequence is markedly dissimilar from other known sea anemones toxins. There are two known genes coding for two highly homologous calitoxins. They are CLX-1 and CLX-2, both consisting of 46 amino acids with three disulfide bonds. Both originate from a precursor peptide of 79 amino acids where the C-terminus determines whether it will be the mature CLX-1 or CLX-2. Researchers consider that these precursors may be stored in cnidocytes. Under the effects of some triggering stimulus, the precursor would be modified and released in the active form. The patterning of cleavage sites targeted during maturation of the peptide suggest that the active quaternary structure might be a tetrapeptide.

In the mature CLX, one base-pair substitution is responsible for a single glutamic acid to lysine replacement in the coding region of CLX-2, leading to the difference between the two peptides. The structural organization of these two genes show a high degree of homology. This might imply that the two different peptides have the same biological function. This cannot yet be confirmed because only CLX-1 has been isolated from C. parasitica. Calitoxin has a low degree of homology another sodium channel binding sea anemone toxin, ATX II, which might offer insights in the function of particular amino acid residues. Despite markedly dissimilar gene sequences, CLX-1 affects crustacean axon potentials similar to two other known classes of sea anemone toxins. Certain aspects of the structure of the CLX genes are found in scorpion toxins as well as other sea anemone toxins that block potassium channels.

Target and mode of action

Calitoxin causes massive neurotransmitter release from the nerve terminals of the neuromuscular junction, which in turn causes a strong muscle contraction and even paralysis. The exact target of calitoxin has not yet been clarified; because it has a similar action on the neuromuscular junction as Anemonia sulcata toxins, Calitoxin has been proposed to slow down the inactivation of voltage-gated sodium channels in motor neurons.

Function in nature

Sea anemones produce toxins, such as calitoxin, in their stinging cells (cnidocytes). These cells contain organelles called nematocysts. When triggered, an envenomation response occurs. This can result in injury to target organisms, including capture of prey, defense against predatory organisms, or against aggressors from within their own species. In a natural setting, C. parasitica establishes a mutualistic relationship with the hermit crab Pagurus bernhardus. The sea anemone identifies shells inhabited by the hermit crab and attaches. Through stings against potential predators, C. parasitica provides protection for the hermit crab. In return, the sea anemone gains an advantage in accessing a broader distribution of food sources, as the crab moves across the ocean floor. Octopuses will avoid shells bearing C. parasitica.

Toxicity

Calitoxin has been tested for activity on the crab Carcinus mediterraneus, by injecting a 0.1 mL solution with 0.2 µg lyophilized CLX of into the hemocoel. This revealed that the toxic unit corresponds to this minimum amount of the toxin inducing muscle contractions in the crab causing paralysis within 1 minute from injection. The LD₅₀ is unknown.

References

1. ^ Cariello, L; de Santis, A; Fiore, F; Piccoli, R; Spagnuolo, A; Zanetti, L; Parente, A (21 Mar 1989). "Calitoxin, a neurotoxic peptide from the sea anemone Calliactis parasitica: amino acid sequence and electrophysiological properties". Biochemistry. 28 (6): 2484–9. PMID 2567180. {{cite journal}}: |access-date= requires |url= (help)
2. ^ Spagnuolo, Antonietta; Zanetti, Laura; Cariello, Lucio; Piccoli, Renata. "Isolation and characterization of two genes encoding calitoxins, neurotoxic peptides from Calliactis parasitica (Cnidaria)". Gene. 138 (1–2): 187–191. doi:10.1016/0378-1119(94)90805-2.
3. ^ Kastin, edited by Abba J. (2006). Handbook of biologically active peptides. Amsterdam: Academic Press. pp. 363–364. ISBN 0-12-369442-6. {{cite book}}: |first1= has generic name (help)
4. Rappuoli, Rino; Montecucco, Cesare (29 May 1997). Guidebook to Protein Toxins and Their Use in Cell Biology. Oxford University Press, UK. pp. 139–. ISBN 978-0-19-154728-7. Retrieved 18 November 2014.
5. Q. Ashton Acton, PhD. "Neurologic Manifestations—Advances in Research and Treatment: 2013 Edition". ScholarlyEditions, 2013. p. 60. Retrieved 18 November 2014.
6. Moran, Yehu; Gordon, Dalia; Gurevitz, Michael (December 2009). "Sea anemone toxins affecting voltage-gated sodium channels – molecular and evolutionary features". Toxicon. 54 (8): 1089–1101. doi:10.1016/j.toxicon.2009.02.028. {{cite journal}}: |access-date= requires |url= (help)
7. John Fish & Susan Fish (2011). "Calliactis parasitica (Couch)". A Student's Guide to the Seashore (3rd ed.). Cambridge University Press. p. 96. ISBN 978-0-521-72059-5.
8. Roger T. Hanlon & John B. Messenger (1998). "Learning and the development of behaviour". Cephalopod Behaviour. Cambridge University Press. pp. 132–148. ISBN 978-0-521-64583-6.

• Invertebrate toxins
• Ion channel toxins