Panorama of the Intracellular Molecular Concert Orchestrated by Actinoporins, Pore-Forming Toxins from Sea Anemones

Abstract

Actinoporins (APs) are soluble pore-forming proteins secreted by sea anemones that experience conformational changes originating in pores in the membranes that can lead to cell death. The processes involved in the binding and pore-formation of members of this protein family have been deeply examined in recent years; however, the intracellular responses to APs are only beginning to be understood. Unlike pore formers of bacterial origin, whose intracellular impact has been studied in more detail, currently, we only have knowledge of a few poorly integrated elements of the APs’ intracellular action. In this review, we present and discuss an updated landscape of the studies aimed at understanding the intracellular pathways triggered in response to APs attack with particular reference to sticholysin II, the most active isoform produced by the Caribbean Sea anemone Stichodactyla helianthus. To achieve this, we first describe the major alterations these cytolysins elicit on simpler cells, such as non-nucleated mammalian erythrocytes, and then onto more complex eukaryotic cells, including tumor cells. This understanding has provided the basis for the development of novel applications of sticholysins such as the construction of immunotoxins directed against undesirable cells, such as tumor cells, and the design of a cancer vaccine platform. These are among the most interesting potential uses for the members of this toxin family that have been carried out in our laboratory.

Advances in Biosensors for the Rapid Detection of Marine Biotoxins: Current Status and Future Perspectives

“…Typically, they are classified based on their chemical structure, origin, and mode of action. The primary classification method is chemical structure, which divides biotoxins into three main types: peptide toxins, polyether toxins, and alkaloid toxins (Table 1) [24][25][26].…”

“…Peptide toxin Conotoxin, sea anemone peptide toxins, sea serpent toxins Taro snails, sea anemones, sea snakes [24][25][26] Polyether toxin Ciguatoxin, rock sand anemone toxin, nudibranch toxin Algae of the genus verbascum gangbytis, short nudibranchs, and sand group anemones [11,27,28] Alkaloid toxin Tetrodotoxin, saxitoxin, genotoxin Puffer fish, shellfish, gonyaulax [29,30] Peptide toxins are a type of small organic compound composed of multiple amino acid molecules, categorized by their chemical structure. Numerous peptide toxins have been identified, with extensively studied examples including conotoxin, sea anemone peptide toxin, and sea snake toxin.…”

Sea Anemones, Actinoporins, and Cholesterol

“…Actinoporins began to be an important subject of study for some of these scientists when, at the end of the 20th century [ 1 , 2 , 3 , 4 ], a Cuban group led by María Eliana Lanio, Fabiola Pazos, and Carlos Álvarez began to spread the word, sending several of their postdocs and students to different labs in Europe [ 5 , 6 ]. In Spain, they came to the Biophysics Institute at Bilbao ( ), led by Félix Goñi and Alicia Alonso, and to our Protein Function and Structure Group (ESFUNPROT; ), funded and directed by José G. Gavilanes, one of the authors of this article.…”

Visible Light Control over the Cytolytic Activity of a Toxic Pore-Forming Protein

“…While some of these inherently toxic proteins have targeting capabilities, such as the latrotoxin of the deadly black widow spider that selectively punctures neurons, , others, like actinoporins, lyse indiscriminately all sphingomyelin-containing membranes. − Since all mammalian cell surfaces contain sphingomyelin, the cytolytic activity of actinoporin PFTs can potentially result in the destruction of human cells. However, to precisely and safely utilize PFTs as novel chemotherapeutics, it is necessary to establish external control over their pore-formation ability.…”