Regulation of G protein signaling for "feeding receptor" melanin-concentrating hormone receptor 1

“进食受体”黑色素浓缩激素受体 1 的 G 蛋白信号传导调节

• 批准号: 17500259
• 负责人: SAITO Yumiko
• 金额: $ 2.24万
• 依托单位: HIROSHIMA UNIVERSITY (2006)Saitama Medical University (2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500259/
• 关键词: feeding; depression; anxiety; signal transduction; G protein; 不安; 肥満; 受容体; 細胞内情報伝達; うつ

Melanin-concentrating hormone (MCH) receptor 1 (MCH1R) is a class A G protein-coupled receptor (GPCR). The MCH system has been linked to a variety of physiological functions, including the regulation of feeding, energy metabolism and stress-induced responses. We have already reported the importance of a dibasic motif in the membrane-proximal C-terminal region for MCH1R function. In this project, we further reveal that an Arg residue in intracellular loop 2 of MCH1R (R155) plays a critical role in receptor function. To purify potential MCH1R interacting proteins from mouse brain, the N-terminus, second intracellular loop (i2), third intracellular loop (i3) or the C terminal tail was expressed as a GST fusion protein and immobilized on glutathione-agarose. MALDI-TOF-MS analysis identified several proteins, and one of protein preferentially interacted with i2 domain was found to belong to Ser/Thr kinase family. In 293T cells that were transiently transfected with MCH1R and the kinase, stimulation of MCH1R by agonist results in the recruitment of the activated kinase from cytoplasm to the plasma membrane, in which the kinase was colocalized with MCH1R. A well-characterized inhibitor for the kinase did significantly interfere MCH-induced internalization. This is the first protein-protein interaction demonstrated to alter agonist-stimulated internalization of the MCH1R.

黑色素浓集激素（MCH）受体1（MCH 1 R）是A类G蛋白偶联受体（GPCR）。MCH系统与多种生理功能有关，包括摄食调节、能量代谢和应激诱导的反应。我们已经报道了一个二元基序在膜近端的C-末端区域的重要性MCH 1 R功能。在本项目中，我们进一步揭示了MCH 1 R（R155）细胞内环2中的Arg残基在受体功能中起着关键作用。为了从小鼠脑中纯化潜在的MCH 1 R相互作用蛋白，将N末端、第二胞内环（i2）、第三环（i3）或C末端尾表达为GST融合蛋白并固定在谷胱甘肽-琼脂糖上。MALDI-TOF-MS分析鉴定了几个蛋白质，其中一个与i2结构域优先相互作用的蛋白质属于Ser/Thr激酶家族。在用MCH 1 R和激酶瞬时转染的293 T细胞中，激动剂对MCH 1 R的刺激导致活化的激酶从细胞质募集到质膜，其中激酶与MCH 1 R共定位。一种经过充分表征的激酶抑制剂确实显着干扰了MCH诱导的内化。这是第一个蛋白质-蛋白质相互作用证明改变激动剂刺激的MCH 1 R的内化。

项目成果

Arginine residue 155 in the second intracellular loop plays a critical rilein rat melanin-concentrating hormone receptor 1 activation

第二个细胞内环中的精氨酸残基 155 对 rilein 大鼠黑色素浓缩激素受体 1 激活起着关键作用

• 发表时间: 2005
• 期刊: Endocrinology 146
• 作者: Saito;Y et al.
• 通讯作者: Y et al.

オーファンGPCRとうつ病

孤儿 GPCR 与抑郁症

• 发表时间: 2006
• 期刊: 日本薬理学雑誌 127
• 作者: Saito;Y. et al.;斎藤祐見子ら
• 通讯作者: 斎藤祐見子ら

Lignan compounds and 4,4'-dihydroxybiphenyl protect C2C12 cells against damage from oxidative stress

木脂素化合物和 4,4-二羟基联苯保护 C2C12 细胞免受氧化应激损伤

• 发表时间: 2006
• 期刊: Biophys Biochem Res Commun. 344
• 作者: Yoshikawa;A.
• 通讯作者: A.

Salusin β is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1

• DOI: 10.1016/j.ejphar.2006.03.064
• 发表时间: 2006-06
• 期刊: European Journal of Pharmacology
• 影响因子: 5
• 作者: Zhiwei Wang;Toshio Takahashi;Yumiko Saito;H. Nagasaki;N. K. Ly;H. Nothacker;R. Reinscheid;Jun Yang;J. Chang;M. Shichiri;O. Civelli

Orphan GPCRs and depression

孤儿 GPCR 和抑郁症

• 发表时间: 2006
• 期刊: Nihon Yakurigaku Zashi 127
• 作者: Saito;Y.;Maruyama;K.
• 通讯作者: K.