IYOR Intern's Take on Singapore's Marine Life - The sea anemones' venomous concoctions

We end this series of science communication with the world of venom in sea anemones. Yes, the tiny cnidae that you read earlier are venomous! No touching!

Soft-bodied and somewhat jelly-like, these sea anemones are packed with great survival skills in the ocean: from evading of predators to microscopic weapons of death. These sea anemones continue to wow as we now learn more about their venomous stinging cells.

Venomous concoctions in sea anemones

The sea ninja’s most potent weapon is its venom. The cnidae of anemones contain a venomous concoction filled with a menagerie of toxins that causes different kinds of physiological effects on their victims. Some anemone toxins viciously destroy cells, while others are responsible for paralysing victims, causing them excruciating pain.

There are three main types of toxic tools in the anemone’s arsenal: enzymes, ripper toxins, and neurotoxins. Enzyme phospholipase A2 systematically disintegrates cell membranes, this not only helps with the destruction of cells, it also helps the sea anemone to digest its prey. Similarly, the skin damage, blisters, and burning sensations caused by touching box jellyfish and hellfire anemones are the result of malicious metalloproteases within the venom. The metalloproteases murder cells by entering into the extracellular matrix and degrading the biochemical network supporting cells.

Diagram of cnidocyte ejecting a nematocyst containing venom. Source: Manoa Hawaii (Byron Inuoye). 

The enzymatic toxins work in tandem with the ripper toxins. Ripper toxins or pore-forming toxins are a standard weapon in most cnidarians' arsenal. Pore-forming toxins target the boundaries of cells, also known as the cell membrane. Cytolysins and actinoporins act as ‘molecular drills’ that form pores (holes) within the cell membrane by inserting the helical part of the toxin into the membrane. The cell then slowly becomes flooded with water and salts until it swells up and bursts like a balloon. Not only do the ripper toxins brutally rupture and slice blood cells, some cytolysins will specifically bind to a specific type of lipid-like sphingomyelin. One of our native anemones, Heteractis magnifica, produces a very potent cytolysin which not only destroys cells in general, but it can specifically target and lyse blood cells.

The Magnificent Anemone (Heteractis magnifica), a common species found in Singapore. Source: Wild Singapore.

Demolishing cells is only one of the effective strategies used by the sea ninja; on one hand, to paralyse the prey, and on the other hand, to stun their predators with neurotoxins. Sea anemones produce a variety of neurotoxins such as potassium channel toxins, sodium channel toxins, and acid-sensing ion channel toxins to target lipid-based membranes in nerve, cardiac, and muscle cells.

Ion channels are important for processes such as generating electric signals within cells. Sodium channel toxins bind to their target and stop the sodium channels from changing its conformation. This causes the sodium channels to become stuck wide open allowing entry of excess sodium ions, which disrupts the balance of ions between the two sides of the membranes. Eventually, leading to spasms and paralysis in their victims. There are some known sodium channel toxins that specifically target arthropods, and no other animals.

An example of the mechanism of animal toxins blocking the potassium channel. Most toxins from animal venoms block the central pore to prevent K+ transport. Source: Zhao et al. (2015).

Potassium channel toxins not only have neurotoxic and cardiotoxic effects, but some potassium channel toxins also have anti-bacterial and anti-viral properties. One of the carpet anemones (Stichodactyla helianthus) produces ShK a potassium channel toxin, which physically blocks the pores of potassium channels and stops the flow of current through the channels. Potassium channel toxin, such as APETx1, target potassium channels found in heart muscle cells by blocking the flow of current within the channel.

The Kunitz potassium channel toxins are multi-taskers: they not only block potassium channels, they also inhibit proteases such as trypsin. This is one the sea ninja’s most clever schemes since Kunitz peptides prevent the degradation of the venom by the enzymes found of the victim. The aggregating anemone (Anthopleura elegantissima) produces a toxin known as APETx2 which targets acid-sensing ion channels and inhibits the channel by modifying the channel. Acid-sensing ion channels play a role in generating pain signals caused by inflammation, which makes them a prime target for drug development.

Stichodactyla helianthus, also known as the Sun Anemones.

The concoction of venoms from the sea ninja sing together in a symphony of suffering. A dash of histamine and serotonin in the venom can drop blood pressure and sharpen the pain. Even though sea anemone venom contains a plethora of potent and fascinating peptides, anemone toxins are understudied. Less than 4 percent of sea anemones have had their venom extracted and studied, which is a pity because sea anemone toxins could provide inspiration for designing novel drugs.

So far, researchers have used cytolysins to target and kill cancer cells. Cytolysins can be used to form pores within the cancer cells, which makes it easier for anti-cancer drugs to enter the glioblastoma cells (aggressive cancer). This is an effective way of controlling the dosage of anti-cancer drugs, and it can help reduce the severe side effects of chemotherapy. A potent potassium blocker isolated from Stichodactyla helianthus (Sun Anemone) was used to develop a drug to treat autoimmune diseases. A lot of diseases is caused by the malfunctioning of ion channels or the wrong type of ion channel being found in certain types of cells. Ion channel toxins isolated from sea anemones can be highly specific and effective, which makes them a fantastic weapon to fight diseases caused by malfunctioning ion channels like multiple sclerosis, psoriasis, etc. 

In conclusion, the venomous concoction of sea anemones not only contains potent toxins which conquer prey and predator alike, it also provides a goldmine of potential drugs which could cure a variety of diseases.

About the writer:
Shabdita Vatsa recently graduated from the National University of Singapore with a Bachelors in Life Sciences (Molecular and Cell Biology). She spent most of her undergraduate days obsessing over sea anemones and their toxins. Her fascination became research projects, working with scientists from the Reef Ecology Lab and Protein Chemistry Lab to study anemone toxins.

A passionate writer, Shabdita loves creative writing, popular science writing, and scientific writing. You can find more of her writings on her personal page: https://lifesciencepotluck.tumblr.com/

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