The retinoic acid receptor (RAR) in molluscs: Function, evolution and endocrine disruption insights. 2019

Ana André, and Raquel Ruivo, and Elza Fonseca, and Elsa Froufe, and L Filipe C Castro, and Miguel M Santos
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208, Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007, Porto, Portugal; ICBAS - Institute of biomedical Sciences Abel Salazar, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313, Porto, Portugal. Electronic address: anaiandre@sapo.pt.

Retinoid acid receptor (RAR)-dependent signalling pathways are essential for the regulation and maintenance of essential biological functions and are recognized targets of disruptive anthropogenic compounds. Recent studies put forward the inability of mollusc RARs to bind and respond to the canonical vertebrate ligand, retinoic acid: a feature that seems to have been lost during evolution. Yet, these studies were carried out in a limited number of molluscs. Therefore, using an in vitro transactivation assay, the present work aimed to characterize phylogenetically relevant mollusc RARs, as monomers or as functional units with RXR, not only in the presence of vertebrate bone fine ligands but also known endocrine disruptors, described to modulate retinoid-dependent pathways. In general, none of the tested mollusc RARs were able to activate reporter gene transcription when exposed to retinoic acid isomers, suggesting that the ability to respond to retinoic acid was lost across molluscs. Similarly, the analysed mollusc RAR were unresponsive towards organochloride pesticides. In contrast, transcriptional repressions were observed with the RAR/RXR unit upon exposure to retinoids or RXR-specific ligands. Loss-of-function and gain-of-function mutations further corroborate the obtained results and suggest that the repressive behaviour, observed with mollusc and human RAR/RXR heterodimers, is possibly mediated by ligand biding to RXR.

UI MeSH Term Description Entries
D008156 Luciferases Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates. Luciferase
D008974 Mollusca A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes GASTROPODA; BIVALVIA; CEPHALOPODA; Aplacophora; Scaphopoda; Polyplacophora; and Monoplacophora. Molluscs,Mollusks,Mollusc,Molluscas,Mollusk
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010802 Phylogeny The relationships of groups of organisms as reflected by their genetic makeup. Community Phylogenetics,Molecular Phylogenetics,Phylogenetic Analyses,Phylogenetic Analysis,Phylogenetic Clustering,Phylogenetic Comparative Analysis,Phylogenetic Comparative Methods,Phylogenetic Distance,Phylogenetic Generalized Least Squares,Phylogenetic Groups,Phylogenetic Incongruence,Phylogenetic Inference,Phylogenetic Networks,Phylogenetic Reconstruction,Phylogenetic Relatedness,Phylogenetic Relationships,Phylogenetic Signal,Phylogenetic Structure,Phylogenetic Tree,Phylogenetic Trees,Phylogenomics,Analyse, Phylogenetic,Analysis, Phylogenetic,Analysis, Phylogenetic Comparative,Clustering, Phylogenetic,Community Phylogenetic,Comparative Analysis, Phylogenetic,Comparative Method, Phylogenetic,Distance, Phylogenetic,Group, Phylogenetic,Incongruence, Phylogenetic,Inference, Phylogenetic,Method, Phylogenetic Comparative,Molecular Phylogenetic,Network, Phylogenetic,Phylogenetic Analyse,Phylogenetic Clusterings,Phylogenetic Comparative Analyses,Phylogenetic Comparative Method,Phylogenetic Distances,Phylogenetic Group,Phylogenetic Incongruences,Phylogenetic Inferences,Phylogenetic Network,Phylogenetic Reconstructions,Phylogenetic Relatednesses,Phylogenetic Relationship,Phylogenetic Signals,Phylogenetic Structures,Phylogenetic, Community,Phylogenetic, Molecular,Phylogenies,Phylogenomic,Reconstruction, Phylogenetic,Relatedness, Phylogenetic,Relationship, Phylogenetic,Signal, Phylogenetic,Structure, Phylogenetic,Tree, Phylogenetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D014212 Tretinoin An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). Retinoic Acid,Vitamin A Acid,Retin-A,Tretinoin Potassium Salt,Tretinoin Sodium Salt,Tretinoin Zinc Salt,Vesanoid,all-trans-Retinoic Acid,beta-all-trans-Retinoic Acid,trans-Retinoic Acid,Acid, Retinoic,Acid, Vitamin A,Acid, all-trans-Retinoic,Acid, beta-all-trans-Retinoic,Acid, trans-Retinoic,Potassium Salt, Tretinoin,Retin A,Salt, Tretinoin Potassium,Salt, Tretinoin Sodium,Salt, Tretinoin Zinc,Sodium Salt, Tretinoin,Zinc Salt, Tretinoin,all trans Retinoic Acid,beta all trans Retinoic Acid,trans Retinoic Acid
D014874 Water Pollutants, Chemical Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water. Chemical Water Pollutants,Landfill Leachate,Leachate, Landfill,Pollutants, Chemical Water

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