The fifth neurohypophysial hormone receptor is structurally related to the V2-type receptor but functionally similar to V1-type receptors
The fifth neurohypophysial hormone receptor is structurally related to the V2-type receptor but functionally similar to V1-type receptors
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DOI：
10.1016/j.ygcen.2012.07.008
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发表时间：
2012-09-15
影响因子：
2.7
通讯作者：
Hyodo, Susumu
中科院分区：
文献类型：
--
作者：
Yamaguchi, Yoko;Kaiya, Hiroyuki;Hyodo, Susumu
加压素(VP)和催产素(OT)家族的神经垂体多肽通过不同的G蛋白偶联受体调节盐和水的动态平衡和生殖。目前认为脊椎动物存在四种神经垂体激素受体(V1aR、V1bR、V2R和OtR)，它们的进化史仍有争议。我们报道了从全头象鱼中鉴定出第五种神经垂体激素受体(V2bR)。该受体在序列上类似于传统的V2R(V2aR)，但在非哺乳动物VP同源蛋白血管催产素(VT)的作用下诱导钙信号转导；这种信号转导是典型的V1型受体。此外，还从象鱼中分离到V1aR、V1bR和OtR。进一步的筛选发现，V2bR基因广泛分布于颌骨脊椎动物，V2bR家族分为两个亚家族：鱼类特有的类型-1和四足动物特有的类型-2。分析表明，哺乳动物的V2bR可能已经失去了功能。基于分子系统发育、共线和功能分析，我们提出了脊椎动物神经垂体激素受体的新的进化史：第一次复制产生了V1aR/V1bR/Otr和V2aR/V2bR谱系，V2aR谱系偏离V2bR谱系后进化为使用cAMP作为第二信使，而V2bRs保留了原始的钙信号系统。未来对V2bR在脑、心、肾和生殖器官中作用的研究将为VP/VT的生理学和进化开辟一个新的研究领域。(C)2012 Elsevier Inc.保留所有权利。
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 Ca2+ 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 Ca2+ 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. (c) 2012 Elsevier Inc. All rights reserved.