University of Guelph, College of Biological Sciences, Integrative Biology, Guelph, ON N1G-2W1, Canada.
Mol Cell Endocrinol. 2022 Jan 1;539:111468. doi: 10.1016/j.mce.2021.111468. Epub 2021 Oct 2.
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.
核受体（NRs）负责调节后生动物中多样化的发育和生理系统。NR 的作用可以是基因组和非基因组机制的结果，这取决于它们分别在核内还是核外起作用。虽然这两种机制的作用都被证明对 NR 功能至关重要，但非基因组作用比基因组作用被认为更少。此外，关于非基因组 NR 信号通路起源和进化的假说在文献中很少被讨论。在这里，我们总结了 NR 蛋白家族进化和动物门水平中非基因组 NR 信号机制。我们发现，不同群组和门水平的 NR 都通过钙流以及蛋白磷酸化级联（MAPK/PI3K/PKC）起作用。我们假设并讨论了包括甲状腺激素受体、维生素 D 受体、蜕皮激素受体、视黄酸受体、甾体激素受体等在内的 NR1 和 NR3 家族 NR 可能具有的共同特征。总之，我们提出，非基因组 NR 信号的出现可能是刺胞动物、扁盘动物和两侧对称动物中 NR 多样性扩展的驱动力。
