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The latrunculins are a family of and produced by certain sea sponge, including genus Latrunculia and Negombata, whence the name is derived. It binds actin monomers near the nucleotide binding cleft with 1:1 stoichiometry and prevents them from polymerize. Administered in vivo, this effect results in disruption of the actin filaments of the cytoskeleton, and allows visualization of the corresponding changes made to the cellular processes. This property is similar to that of cytochalasin, but has a narrow effective concentration range. Latrunculin has been used to great effect in the discovery of cadherin distribution regulation and has potential medical applications. Latrunculin A, a type of the toxin, was found to be able to make reversible morphological changes to mammalian cells by disrupting the actin network.
Latrunculin A:
Gelsolin - Latrunculin A causes end- blocking; this protein binds to the barbed sides of the actin filaments which accelerates nucleation. This calcium-regulated protein also plays a role in assembly and disassembly of cilia which plays a crucial role in handedness.
Latrunculin B:
| Molecular Formula: | C20H29NO5S[Latrunculin#cite]] |
| Molecular Weight: | 395.514 g/mol |
Actin- Latrunculin B makes up the structure of the actin fibers.
Protein spire homolog 2- needed for cell division, vesicle transport within the actin filament and is essential for the formation of the cleavage formation during cell division[Latrunculin#cite]].
Latrunculin makes up to 0.35% of the dry weight of the sponge. There are two main forms of the toxin, A and B. Latrunculin A is only present in sponges which live in the Gulf of Suez while latrunculin B only exist in sponges in the Gulf of Aqaba. Why this is the case is still under investigation.
Experimental evidence shows that latruculin-A is biologically active in the solvent DMSO, but not in aqueous solutions, as demonstrated in cell culture and in brain tissue probably due to cellular permeation.
When actin is impaired due to latrunculin, have a better chance of infiltrating the intestinal epithelial monolayer in Escherichia coli, which may cause a higher chance of generating gastrointestinal illnesses.
It seems that actin monomers are more sensitive to bind latrunculin A than to bind Latrunculin B. In other words, latrunculin A is a more potent toxin. Latrunculin B is inactivated faster than latrunculin A.
The prevention of polymerizing of the actin filaments causes reversible changes in the morphology of mammalian cells. Lantranculin interferes with the structure of the cytoskeleton in rats.
After latrunculin B exposure, mouse fibroblasts grow bigger and PtK2 kidney cells from a potoroo stem produced long, branched extensions. The extensions seem to be an accumulation of actin monomers.
Yeast mutants that are resistant to latrunculin show a mutation, D157E, that initiates a hydrogen bond with latrunculin. Other yeast mutants adjust the binding site, thus making it resistant to latrunculin.
No research has been done to figure out how the biotransformation of latrunculin works in eukaryotic cells. However, research suggests that it is the unaltered form of latrunculin that causes toxic effects.
Adding latrunculin B to solutions of pollen Actin resulted in a rapid decrease in the total amount of polymer, with the extent of depolymerization increasing with the concentration of the toxin. The concentration of latrunculin B required for half-maximal inhibition of pollen germination is 40 to 50 nM. In contrast, pollen tube extension is much more sensitive, requiring only 5 to 7 nM LATB for half-maximal inhibition. The disruption of germination and pollen tube growth by latrunculin B is partially reversible at low concentrations. (<30 nM).
Latrunculin A has been used as acrosome reaction inhibitor of guinea pig in laboratory conditions.
| Indicator | Species | Dose |
| Oral TDLO | Man | 1,14 ml/kg, 650 mg/kg |
| Oral LD50 | Rat | 7,06 mg/kg |
| Oral LD50 | Mouse | 3,45 g/kg, 10,5 ml/kg |
| Oral LD50 | Rabbit | 6,30 mg/kg |
| Inhalation LC50 | Rat | 6h: 5,900 mg/m3
10h: 20,000 ppm |
| Inhalation LCLO | Mouse | 7h: 29,300 ppm |
| Inhalation TCLO | Human | 20m: 2,500 mg/m3
30m: 1,800 ppm |
| Irritation eyes | Rabbit | 24h: 500 mg |
| Irritation skin | Rabbit | 24h: 20 mg |
Latrunculins are produced for fundamental research and have potential medical applications as latrunculins and their derivatives show antiangionic, antiproliferative, antimicrobial and antimetastatic activities.
The sponges themselves are not damaged by latrunculin. As a measure against self-toxination, they keep the latrunculin in membrane-bound , that also function as secretory and storage vesicles. These vacuoles are free of actin and prevent the latrunculin from entering the cytosol where it would damage actin. After production in the Choanocyte, the latrunculin is transferred via the Archaeocyte to the vulnerable areas of the sponges where defense is needed, such as injured or regenerating sites.
In 2015, the discovery that five closely related sea slugs of the genus Chromodoris all use latrunculin as defense, indicates that the toxic might be used via Müllerian mimicry.
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