Is a Modified Actin the Key to Toxin Resistance in the Nudibranch <em>Chromodoris</em>? A Biochemical and Molecular Approach
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
Affiliations
Cora Hertzer
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany
Nani Ingrid Jacquline Undap
Leibniz Institute for the Analysis of Biodiversity Change, Museum Koenig Bonn, Adenauerallee 160, 53113 Bonn, Germany
Adelfia Papu
Leibniz Institute for the Analysis of Biodiversity Change, Museum Koenig Bonn, Adenauerallee 160, 53113 Bonn, Germany
Dhaka Ram Bhandari
Institute of Inorganic and Analytical Chemistry, Justus-Liebig-University, Heinrich-Buff-Ring 17, 35392 Gießen, Germany
Stefan Aatz
Institute of Biochemistry and Molecular Biology, University of Bonn, Nussallee 11, 53115 Bonn, Germany
Stefan Kehraus
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany
Fontje Kaligis
Faculty of Fisheries and Marine Science, Sam Ratulangi University, Jl. Kampus UNSRAT Bahu, Manado 95115, Sulawesi Utara, Indonesia
Robert Bara
Faculty of Fisheries and Marine Science, Sam Ratulangi University, Jl. Kampus UNSRAT Bahu, Manado 95115, Sulawesi Utara, Indonesia
Till F. Schäberle
Institute for Insect Biotechnology, Justus-Liebig-University and Department for Bioresources of the Fraunhofer Institute for Molecular Biology and Applied Ecology, Ohlebergsweg 12, 35392 Gießen, Germany
Heike Wägele
Leibniz Institute for the Analysis of Biodiversity Change, Museum Koenig Bonn, Adenauerallee 160, 53113 Bonn, Germany
Gabriele M. König
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany
Five Chromodoris 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 Chromodoris species, as well as in one of the associated sponges Cacospongia mycofijiensis (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. In vivo toxicity experiments with the sacoglossan Elysia viridis (Montagu, 1804) showed 100% mortality, but 100% survival of Chromodoris specimens, demonstrating resistance to LatA. A novel actin isoform was detected in all investigated Chromodoris 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.
