A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms

Area of Science:

• Endocrinology
• Evolutionary Biology
• Toxicology

Background:

• Nuclear receptors (NRs) are vital for metazoan endocrine systems, particularly the VDR/PXR/CAR (NR1I/J) group involved in detoxification.
• Vertebrate NR1I/J orthologues are well-studied, but knowledge of their invertebrate counterparts remains limited.

Purpose of the Study:

• To isolate and characterize the first lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J) from the bivalve Scrobicularia plana.
• To investigate the xenobiotic receptor plasticity of this molluscan NR1Jβ by comparing its response to human PXR.
• To explore gene duplication and loss patterns within NR gene families in protostomes.

Main Methods:

• Isolation and characterization of the Scrobicularia plana NR1Jβ nuclear receptor.
• Reporter gene assays to evaluate xenobiotic responses.
• Comparative analysis with human PXR.

Main Results:

• The Scrobicularia plana NR1Jβ responded to the natural toxin okadaic acid similarly to other invertebrates.
• Esfenvalerate pesticide uniquely down-regulated transactivation at higher concentrations; triclosan elicited no response.
• Evidence of lineage-specific gene duplications and losses in protostome NR genes was found.

Conclusions:

• The study provides the first characterization of a protostome NR1J receptor, expanding our understanding of invertebrate detoxification pathways.
• Observed xenobiotic responses highlight the plasticity and specificity of molluscan nuclear receptors.
• The findings suggest significant evolutionary variation in NR complexity across protostome lineages and offer potential for developing novel biosensor tools.