Department of Biological Science, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
Department of Biological Science, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
Gen Comp Endocrinol. 2020 Dec 1;299:113586. doi: 10.1016/j.ygcen.2020.113586. Epub 2020 Aug 20.
Urotensin II (UII) is involved, via the UII receptor (UTR), in many physiological and pathological processes, including vasoconstriction, locomotion, osmoregulation, immune response, and metabolic syndrome. In silico studies have revealed the presence of four or five distinct UTR (UTR1-UTR5) gene sequences in nonmammalian vertebrates. However, the functionality of these receptor subtypes and their associations to signaling pathways are unclear. In this study, full-length cDNAs encoding four distinct UTR subtypes (UTR1, UTR3, UTR4, and UTR5) were isolated from the western clawed frog (Xenopus tropicalis). In functional analyses, homologous Xenopus UII stimulation of cells expressing UTR1 or UTR5 induced intracellular calcoum mobilization and phosphorylation of extracellular signal-regulated kinase 1/2. Cells expressing UTR3 or UTR4 did not show this response. Furthermore, UII induced the phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) through the UII-UTR1/5 system. However, intracellular cAMP accumulation was not observed, suggesting that UII-induced CREB phosphorylation is caused by a signaling pathway different from that involving Gs protein. In contrast, the administration of UII to cells increased the phosphorylation of guanine nucleotide exchange factor-H1 (GEF-H1) and myosin light chain 2 (MLC2) in all UTR subtypes. These results define four distinct UTR functional subtypes and are consistent with the molecular evolution of UTR subtypes in vertebrates. Further understanding of signaling properties associated with UTR subtypes may help in clarifying the functional roles associated with UII-UTR interactions in nonmammalian vertebrates.
尿鸟素 II（UII）通过 UII 受体（UTR）参与许多生理和病理过程，包括血管收缩、运动、渗透压调节、免疫反应和代谢综合征。计算机模拟研究表明，在非哺乳动物脊椎动物中存在四种或五种不同的 UTR（UTR1-UTR5）基因序列。然而，这些受体亚型的功能及其与信号通路的关联尚不清楚。在这项研究中，从西部爪蟾（Xenopus tropicalis）中分离出编码四个不同 UTR 亚型（UTR1、UTR3、UTR4 和 UTR5）的全长 cDNA。在功能分析中，同源的 Xenopus UII 刺激表达 UTR1 或 UTR5 的细胞诱导细胞内钙动员和细胞外信号调节激酶 1/2 的磷酸化。表达 UTR3 或 UTR4 的细胞没有显示出这种反应。此外，UII 通过 UII-UTR1/5 系统诱导环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化。然而，没有观察到细胞内 cAMP 积累，这表明 UII 诱导的 CREB 磷酸化是由不同于涉及 Gs 蛋白的信号通路引起的。相比之下，向细胞中给予 UII 会增加所有 UTR 亚型中鸟嘌呤核苷酸交换因子-H1（GEF-H1）和肌球蛋白轻链 2（MLC2）的磷酸化。这些结果定义了四个不同的 UTR 功能亚型，与脊椎动物 UTR 亚型的分子进化一致。进一步了解与 UTR 亚型相关的信号特性可能有助于阐明与非哺乳动物脊椎动物 UII-UTR 相互作用相关的功能作用。
