Muscle regulatory factors regulate T1R3 taste receptor expression
Muscle regulatory factors regulate T1R3 taste receptor expression
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DOI：
10.1016/j.bbrc.2015.10.142
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发表时间：
2015-12-25
影响因子：
3.1
通讯作者：
Yoda, Tetsuya
中科院分区：
文献类型：
--
作者：
Kokabu, Shoichiro;Lowery, Jonathan W.;Yoda, Tetsuya
T1 R3是G蛋白偶联受体的T1 R类，当与T1 R1复合时构成鲜味受体的亚基。T1 R3最初在味觉组织中发现，但现在已知在多种组织和细胞类型中表达，例如肠、胰腺β细胞、骨骼肌和心脏。除了味觉识别，T1 R1/T1 R3复合物还作为氨基酸传感器发挥作用，并被认为是激素分泌的控制机制，如胆囊收缩素，胰岛素和十二指肠HCO 3-，并激活哺乳动物雷帕霉素复合物1（MTORC 1）以抑制自噬。T1 R3基因敲除小鼠在心脏、骨骼肌和肝脏中的自噬率增加。因此，T1 R3具有多种生理功能，并在体内广泛表达。然而，调节T1 R3表达的确切机制在很大程度上是未知的。在这里，我们使用比较基因组学和功能分析来表征人类T1 R3的注释转录起始上游的基因组区域。这表明，T1 R3启动子在人类和小鼠中位于进化保守区（ECR）。我们还确定了一个阻遏元件位于人类T1 R3启动子的上游，具有相对较高的恒河猴的保守程度。此外，肌细胞生长调节因子MyoD和Myogenin调节T1 R3的表达，并且T1 R3的表达随着小鼠成肌细胞C2 C12的骨骼肌分化而增加，我们的研究提示MyoD和Myogenin可能通过调节T1 R3启动子活性来控制骨骼肌的代谢和稳态。(C)2015 Elsevier Inc. All rights reserved.
T1 R3 is a T1 R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic beta-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3- and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown.Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells.Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity. (C) 2015 Elsevier Inc. All rights reserved.