Is a Modified Actin the Key to Toxin Resistance in the Nudibranch <em>Chromodoris</em>? A Biochemical and Molecular Approach
2023
Cora Hertzer | Nani Ingrid Jacquline Undap | Adelfia Papu | Dhaka Ram Bhandari | Stefan Aatz | Stefan Kehraus | Fontje Kaligis | Robert Bara | Till F. Schäberle | Heike Wägele | Gabriele M. König
Five <i>Chromodoris</i> species from North Sulawesi, Indonesia, were investigated for their sequestration of marine natural products. The cytotoxic 2-thiazolidinone macrolide latrunculin A (LatA) was the major metabolite in all examined <i>Chromodoris</i> species, as well as in one of the associated sponges <i>Cacospongia mycofijiensis</i> (Kakou, Crews & Bakus, 1987), supporting a dietary origin of LatA. Furthermore, LatA was secreted with the mucus trail, suggesting a possible use in short-range chemical communication. MALDI MS-Imaging revealed an accumulation of LatA throughout the mantle tissue, mucus glands, and especially in vacuoles of the mantle dermal formations (MDFs). Cytotoxicity of the isolated LatA was tested in HEK-293 cells, confirming that LatA targets the actin cytoskeleton. <i>In vivo</i> toxicity experiments with the sacoglossan <i>Elysia viridis</i> (Montagu, 1804) showed 100% mortality, but 100% survival of <i>Chromodoris</i> specimens, demonstrating resistance to LatA. A novel actin isoform was detected in all investigated <i>Chromodoris</i> species with two amino acid substitutions at the ‘nucleotide binding’ cleft, the binding site of LatA. These are suggested to cause insensitivity against LatA, thus enabling the storage of the toxin within the body for the slugs’ own defense.
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