Uncovering the diversity of invertebrate nuclear receptors ligands.

The identification of the first nuclear receptors (NRs) several decades ago opened up new avenues for the study of a wide range of physiological processes. Although vertebrate receptors were first to be identified, studies in invertebrates were integral to establishing their transcriptional roles. The determination of 3D structures as well as advances in transcriptomic and proteomic techniques, have also been important in enhancing understanding of NR functions. Structural models and docking studies are the first step towards the discovery of invertebrate NR ligands as well as to understanding the binding properties of these NRs. The objective of this work is to review the NR ligands of invertebrates, specifically retinoids, steroids, fatty acids and phospholipids, bile acids and vitamin D, tyrosine derivatives and porphyrins. Non-typical NR ligands such as metals and gases are also described. We also address structural and evolutionary aspects. Exploring the ligands of invertebrate nuclear receptors, whether endogenous or exogenous, is a strategy that enables us to understand the role these receptors play in the biology of these organisms, as well as to uncover metabolic pathways that are not yet fully understood.