Nuclear receptors (NRs) are responsible for the regulation of diverse developmental and physiological systems in metazoans. NR actions can be the result of genomic and non-genomic mechanisms depending on whether they act inside or outside of the nucleus respectively. While the actions of both mechanisms have been shown to be crucial to NR functions, non-genomic actions are considered less frequently than genomic actions. Furthermore, hypotheses on the origin and evolution of non-genomic NR signaling pathways are rarely discussed in the literature. Here we summarize non-genomic NR signaling mechanisms in the context of NR protein family evolution and animal phyla. We find that NRs across groups and phyla act via calcium flux as well as protein phosphorylation cascades (MAPK/PI3K/PKC). We hypothesize and discuss a possible synapomorphy of NRs in the NR1 and NR3 families, including the thyroid hormone receptor, vitamin D receptor, ecdysone receptor, retinoic acid receptor, steroid receptors, and others. In conclusion, we propose that the advent of non-genomic NR signaling may have been a driving force behind the expansion of NR diversity in Cnidarians, Placozoans, and Bilaterians.
Keywords: Hormone; MAPK; NHR; NR; PI3K; PKC; Steroid; Thyroid; Transcription; Vitamin.
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