title: A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms.
abstract: The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.
authors.affiliation: ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto, Portugal; CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal. Electronic address: catarinarcruzeiro@hotmail.com.
authors.forename: Catarina
authors.initials: C
authors.lastname: Cruzeiro
authors.affiliation: ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto, Portugal; CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal. Electronic address: monicaslm@hotmail.com.
authors.forename: Mónica
authors.initials: M
authors.lastname: Lopes-Marques
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal. Electronic address: ruivo.raquel@gmail.com.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ruivo
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal. Electronic address: nadia.oliveira@ciimar.up.pt.
authors.forename: Nádia
authors.initials: N
authors.lastname: Rodrigues-Oliveira
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal; FCUP - Faculty of Sciences, Department of Biology, U. Porto, Portugal. Electronic address: santos@ciimar.up.pt.
authors.forename: Miguel M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto, Portugal; CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal. Electronic address: mjsrocha@netcabo.pt.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Rocha
authors.affiliation: ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto, Portugal; CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal. Electronic address: erocha@icbas.up.pt.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rocha
authors.affiliation: CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto, Portugal; FCUP - Faculty of Sciences, Department of Biology, U. Porto, Portugal. Electronic address: filipe.castro@ciimar.up.pt.
authors.forename: L Filipe C
authors.initials: LF
authors.lastname: Castro
mesh_terms: D000818:Animals; D017930:Genes, Reporter / Q000235:genetics; D008658:Inactivation, Metabolic / Q000235:genetics*; D008974:Mollusca / Q000235:genetics* / Q000378:metabolism*; D019319:Okadaic Acid / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014874:Water Pollutants, Chemical; D019319:Okadaic Acid
keywords: Molluscs; Nuclear receptors; Okadaic acid; Pesticides; VDR/PXR/CAR