Laboratory of Physiology, Atmosphere and Ocean Research Institute, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8564, Japan.
Gen Comp Endocrinol. 2012 Sep 15;178(3):519-28. doi: 10.1016/j.ygcen.2012.07.008. Epub 2012 Jul 16.
The neurohypophysial peptides of the vasopressin (VP) and oxytocin (OT) families regulate salt and water homeostasis and reproduction through distinct G protein-coupled receptors. The current thinking is that there are four neurohypophysial hormone receptors (V1aR, V1bR, V2R, and OTR) in vertebrates, and their evolutionary history is still debated. We report the identification of a fifth neurohypophysial hormone receptor (V2bR) from the holocephalan elephant fish. This receptor is similar to conventional V2R (V2aR) in sequence, but induced Ca(2+) signaling in response to vasotocin (VT), the non-mammalian VP ortholog; such signaling is typical of V1-type receptors. In addition, V1aR, V1bR and OTR were also isolated from the elephant fish. Further screening revealed that orthologous V2bRs are widely distributed throughout the jawed vertebrates, and that the V2bR family is subdivided into two subfamilies: the fish specific type-1, and a type-2 that is characteristically found in tetrapods. Analysis suggested that the mammalian V2bR may have lost its function. Based on molecular phylogenetic, synteny and functional analyses, we propose a new evolutionary history for the neurohypophysial hormone receptors in vertebrates as follows: the first duplication generated V1aR/V1bR/OTR and V2aR/V2bR lineages; after divergence from the V2bR lineage, the V2aRs evolved to use cAMP as a second messenger, while the V2bRs retained the original Ca(2+) signaling system. Future studies on the role of V2bR in the brain, heart, kidney and reproductive organs, in which it is highly expressed, will open a new research field in VP/VT physiology and evolution.
神经垂体肽家族中的血管加压素 (VP) 和催产素 (OT) 通过不同的 G 蛋白偶联受体调节盐和水的稳态和生殖。目前的观点是，脊椎动物中有四种神经垂体激素受体（V1aR、V1bR、V2R 和 OTR），它们的进化历史仍存在争议。我们从全头鱼中鉴定出第五种神经垂体激素受体（V2bR）。该受体在序列上与传统的 V2R（V2aR）相似，但对非哺乳动物 VP 同源物血管加压素（VT）诱导 Ca(2+)信号；这种信号是典型的 V1 型受体。此外，还从全头鱼中分离出了 V1aR、V1bR 和 OTR。进一步筛选表明，同源 V2bR 广泛分布于有颌脊椎动物中，并且 V2bR 家族分为两个亚家族：鱼类特有的 1 型和在四足动物中特有的 2 型。分析表明，哺乳动物 V2bR 可能已经失去了功能。基于分子系统发育、基因同线性和功能分析，我们提出了一个新的有颌脊椎动物神经垂体激素受体进化史：第一次复制产生了 V1aR/V1bR/OTR 和 V2aR/V2bR 谱系；在与 V2bR 谱系分化后，V2aRs 进化为使用 cAMP 作为第二信使，而 V2bRs 保留了原始的 Ca(2+)信号系统。未来对 V2bR 在高度表达的大脑、心脏、肾脏和生殖器官中的作用的研究将在 VP/VT 生理学和进化方面开辟一个新的研究领域。
