Structural and functional analysis of two novel somatostatin receptors identified from topmouth culter (Erythroculter ilishaeformis)

文献类型： 外文期刊

第一作者： Dong, Haiyan

作者： Dong, Haiyan;Xie, Chao;Zhu, Xiaoxuan;Sun, Chao;Fu, Qianwen;Pan, Lei;Wu, Mengting;Guo, Yinghan;Sun, Jianwei;Shen, Hong;Dong, Haiyan;Ye, Jinyun;Wei, Yunhai

作者机构：

关键词： Somatostatin 14; Somatostatin receptor 6; Somatostatin receptor 7; 17 beta-estradiol; Microcystin-LR

期刊名称：COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY （ 影响因子：3.228； 五年影响因子：3.289 ）

ISSN： 1532-0456

年卷期： 2018 年 210 卷

页码：

收录情况： SCI

摘要： In the present study, we cloned and characterized two somatostatin (SS) receptors (SSTRs) from topmouth culter (Erythroculter ilishaeformis) designated as EISSTR6 and EISSTR7. Analysis of EISSTR6 and EISSTR7 signature motifs, 3D structures, and homology with the known members of the SSTR family indicated that the novel receptors had high similarity to the SSTRs of other vertebrates. EISSTR6 and EISSTR7 mRNA expression was detected in 17 topmouth culter tissues, and the highest level was observed in the pituitary. Luciferase reporter assay revealed that SS14 significantly inhibited forskolin-stimulated pCRE-luc promoter activity in HEK293 cells transiently expressing EISSTR6 and EISSTR7, indicating that the receptors can be activated by SS14. We also identified phosphorylation sites important for the functional activity of EISSTR6 and EISSTR7 by mutating Ser(23,) (43, 507, 196, 311) and Ser(7, 29, 61, 222, 225) residues, respectively, to Ala, which significantly reduced the inhibitory effects of SS14 on the CRE promoter mediated by EISSTR6 and EISSTR7. Furthermore, treatment of juvenile topmouth culters with microcystin-LR or 17 beta-estradiol significantly affected EISSTR6 and EISSTR7 transcription in the brain, liver and spleen, suggesting that these receptors may be involved in the pathogenic mechanisms induced by endocrine disruptors. Our findings should contribute to the understanding of the structure-function relationship and evolution of the SSTR family.

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