Identification of the regulating molecules for the melanin-concentrating hormone receptor 1 that is specifically involved in feeding and depression.

• Project/Area Number: 20500337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hiroshima University
• Principal Investigator: SAITO Yumiko Hiroshima University, 大学院・総合科学研究科, 教授 (00215568)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: G蛋白質共役型受容体 / 摂食 / 細胞内情報伝達 / 構造活性相関 / うつ / G蛋白質 / 情報伝達 / Gタンパク質

Research Abstract

Melanin-concentrating hormone receptor 1 (MCHR1) is a G protein-coupled receptor (GPCR) that is highly expressed in the central nervous system. Extensive studies of genetically engineered animals and selective antagonists showed an important role of MCHR1 in the regulation of many physiological functions including energy homeostasis and emotional processing. By analyzing the effect of a series of site-directed mutations of rat MCHR1 on receptor conformational changes, we found that DRY in i2 loop and Phe318 in helix 8 of MCHR1 are the structurally critical site for receptor dynamics. We further identified three RGS proteins that negatively modulated MCHR1-mediated signaling by acting as GTPase-activating manner. These results will help to better understand the complex mechanism for MCHR1 activation.

Research Products

• [Journal Article] 新規生理活性ペプチドの探索方法の進歩 (2011)
  • Author(s): 児島将康, 斎藤祐見子
  • Journal Title: 実験医学増刊号「代謝制御と内分泌ネットワーク」 29 Pages: 14-22
• [Journal Article] MCHの最新の話題 (2011)
  • Author(s): 斎藤祐見子
  • Journal Title: 実験医学増刊号「代謝制御と内分泌ネットワーク」 29 Pages: 54-59
• [Journal Article] 日本における生理活性ペプチド研究の流れとその展開 (2011)
  • Author(s): 斎藤祐見子, 児島将康
  • Journal Title: 実験医学増刊号「代謝制御と内分泌ネットワーク」 29 Pages: 80-85
• [Journal Article] MCH「摂食制御の分子過程」 (2011)
  • Author(s): 長崎弘, 斎藤祐見子
  • Journal Title: 生体の科学 62 Pages: 37-43
• [Journal Article] Inhibiting roles of melanin-concentrating hormone for skin pigment dispersion in barfin flounder, Verasper moseri. (2011)
  • Author(s): Mizusawa K
  • Journal Title: General and comparative endocrinology. Volume: 171 Pages: 75-81
  • Peer Reviewed
• [Journal Article] MCH (2011)
  • Author(s): 長崎弘
  • Journal Title: 生体の科学「摂食制御の分子過程」 Volume: 62 Pages: 37-43
• [Journal Article] 日本における生理活性ペプチド研究の流れとその展開 (2011)
  • Author(s): 児島将康
  • Journal Title: 実験医学増刊号「代謝・内分泌ネットワークと医薬応用」 Volume: 29 Pages: 14-22
• [Journal Article] MCHの最新の話題 (2011)
  • Author(s): 斎藤祐見子
  • Journal Title: 実験医学増刊号「代謝・内分泌ネットワークと医薬応用」 Volume: 29 Pages: 54-59
• [Journal Article] 日本における生理活性ペプチド研究の流れとその展開 (2011)
  • Author(s): 斎藤祐見子
  • Journal Title: 実験医学増刊号「代謝・内分泌ネットワークと医薬応用」 Volume: 29 Pages: 80-85
• [Journal Article] Functional interaction of regulator of G-protein-signaling-2 with melanin concentrating hormone receptor 1. (2010)
  • Author(s): Miyamoto-Matsubara M, Saito Y.
  • Journal Title: Ann NY Science. 1200 Pages: 112-119
  • Peer Reviewed
• [Journal Article] オーファンGPCR標的創薬-MCH受容体の場合-最新・G蛋白質共役受容体研究-疾患解明とシグナル制御の新時代 (2010)
  • Author(s): 斎藤祐見子
  • Journal Title: 医学のあゆみ 233,9 Pages: 687-691
• [Journal Article] MCH「肥満症(第2版-基礎・臨床研究の進歩」 (2010)
  • Author(s): 斎藤祐見子
  • Journal Title: 日本臨床 68 Pages: 125-128
• [Journal Article] MCH(メラニン凝集ホルモン)日本臨床増刊 (2010)
  • Author(s): 長崎弘, 斎藤祐見子
  • Journal Title: 血液・尿化学検査・免疫学的検査(第7版) 4 Pages: 230-233
• [Journal Article] Identification, localization, and function of a novel avian hypothalamic neuropeptide, 26RFa, and its cognate receptor, G Protein-Coupled Receptor-103. (2010)
  • Author(s): Ukena K
  • Journal Title: Endocrinology Volume: 151 Pages: 2255-2264
  • Peer Reviewed
• [Journal Article] Functional interaction of regulator of G-protein-signaling-2 with melanin-concentrating hormone receptor 1. (2010)
  • Author(s): Miyamoto-Matsubara M
  • Journal Title: Ann NY Science Volume: 1200 Pages: 112-119
  • Peer Reviewed
• [Journal Article] MCH (2010)
  • Author(s): 斎藤祐見子
  • Journal Title: 日本臨床「肥満症(第2版-基礎・臨床研究の進歩」 Volume: 68 Pages: 125-128
• [Journal Article] オーファンGPCR標的創薬-MCH受容体の場合- (2010)
  • Author(s): 斎藤祐見子
  • Journal Title: 医学のあゆみ 「最新・G蛋白質共役受容体研究-疾患解明とシグナル制御の新時代」 Volume: 233 Pages: 687-691
• [Journal Article] MCH(メラニン凝集ホルモン) (2010)
  • Author(s): 長崎弘
  • Journal Title: 日本臨床増刊血液・尿化学検査・免疫学的検査(第7版)4:230-233 Volume: 4 Pages: 230-233
• [Journal Article] Functional interaction of regulator of G-protein-signaling-2 with melanin-concentrating hormone receptor 1 (2010)
  • Author(s): Mayumi Miyamoto-Matsubara
  • Journal Title: Ann NY Science (印刷中)
  • Peer Reviewed
• [Journal Article] Identification, localization, and function of a novel avian hypothalamic neuropeptide, 26RFa, and its cognate receptor, G Protein-Coupled Receptor-103 (2010)
  • Author(s): Kazuyoshi Ukena
  • Journal Title: Endocrinology 151(印刷中)
  • Peer Reviewed
• [Journal Article] MCH (2010)
  • Author(s): 斎藤祐見子
  • Journal Title: 「肥満症(第2版-基礎・臨床研究の進歩」日本臨床 68 Pages: 125-128
• [Journal Article] オーファンGPCR標的創薬-MCH受容体の場合- (2010)
  • Author(s): 斎藤祐見子
  • Journal Title: 最新・G蛋白質共役受容体研究-疾患解明とシグナル制御の新時代 医学のあゆみ (印刷中)
• [Journal Article] Molecular cloning and expression of 2 melanin-concentrating hormone receptors in goldfish. (2009)
  • Author(s): Mizusawa K, Saito Y, Wang Z, Kobayashi Y, Matsuda K, Takahashi A.
  • Journal Title: Peptides 30 Pages: 1990-1996
  • Peer Reviewed
• [Journal Article] Distinct role of the DRY motif in rat melanin-concentrating hormone receptor 1 in signaling control. (2009)
  • Author(s): Aizaki Y, Nakano-Tetsuka M, Maruyama K, Saito Y.
  • Journal Title: Peptides 30 Pages: 974-981
  • NAID: 120001107860
  • Peer Reviewed
• [Journal Article] The pharmacological properties of a novel MCHR1eceptor antagonist isolated from combinatorial libraries. (2009)
  • Author(s): Nagasaki H, Chung S, Dooley CT, Wang Z, Li C, Saito Y, Clark SD, Houghten RA, Civelli O.
  • Journal Title: Eur J Pharmacol. 602 Pages: 194-202
  • Peer Reviewed
• [Journal Article] MCH receptors/gene structure-in vivo expression. (2009)
  • Author(s): Chung S, Saito Y, Civelli O.
  • Journal Title: Peptides 30 Pages: 1985-1989
  • Peer Reviewed
• [Journal Article] Distinct role of the DRY motif in rat melanin-concentrating hormone receptor 1 in signaling control (2009)
  • Author(s): Yoshimi Aizaki
  • Journal Title: Peptides 30 Pages: 974-981
  • Peer Reviewed
• [Journal Article] Molecular cloning and expression of 2 melanin-concentrating hormone receptors in goldfish (2009)
  • Author(s): Kanta Mizusawa
  • Journal Title: Peptides 30 Pages: 1990-1996
  • Peer Reviewed
• [Journal Article] MCH receptors/gene structure-in vivo expression (2009)
  • Author(s): Shinjae Chung
  • Journal Title: Peptides 30 Pages: 1985-1989
  • Peer Reviewed
• [Journal Article] TH2 cytokines potently induce an orexigenicpeptide, melanin-concentrating hormone, in human vascular endothelial cells (2009)
  • Author(s): Kanami Orihara
  • Journal Title: Journal of Allergy and Clinical Immunology 124 Pages: 612-614
  • Peer Reviewed
• [Journal Article] Melanin-concentrating hormone reduces somatolactin release from the cultured goldfish pituitary cells in vitro (2009)
  • Author(s): Mio Tanaka
  • Journal Title: Journal of Endocrinology 203 Pages: 389-398
  • Peer Reviewed
• [Journal Article] Distinct role of the DRY motif in rat melanin-concentrating hormone receptor 1 in signaling control. (2009)
  • Author(s): Yoshimi Aizaki
  • Journal Title: Peptides (印刷中)
  • Peer Reviewed
• [Journal Article] Regulation of melanin-concentrating hormone receptor 1 signaling by RGS8 with the receptor third intracellular loop. (2008)
  • Author(s): Miyamoto-Matsubara M, Saitoh O, Maruyama K, Aizaki Y, Saito Y.
  • Journal Title: Cellular Signaling 20 Pages: 2084-2094
  • NAID: 120001092481
  • Peer Reviewed
• [Journal Article] オーファンG蛋白質共役型受容体研究の進歩 (2008)
  • Author(s): 斎藤祐見子
  • Journal Title: 比較内分泌 34 Pages: 24-28
• [Journal Article] オーファンGPCRの使い方-これまで、そしてこれから- (2008)
  • Author(s): 斎藤祐見子
  • Journal Title: ファルマシア(日本薬学会誌) 44 Pages: 135-139
• [Journal Article] The Melanin-Concentrating Hormone System and Its Physiological Functions (2008)
  • Author(s): Saito, Y, Nagasaki H,
  • Journal Title: Results and Problems in Cell Differentiation : Orphan G protein-coupled receptors and novel neuropeptides(Eds.Civelli/Zhou, Springer Berlin/Heidelberg) 46 Pages: 159-179
  • Peer Reviewed
• [Journal Article] Orphan neuropetides and the regulation of food intake (2008)
  • Author(s): Nagasaki H,, Xy Y, Saito Y, Civelli O.
  • Journal Title: New Frontiers in Lifestyle Related Diseases(Eds. Miyazaki/Imawari, Springer-Verlag Tokyo, Inc.) Pages: 3-19
• [Journal Article] The Melanin-concentrating hormone system and its physiological functions (2008)
  • Author(s): Yumiko Saito
  • Journal Title: Results and Problems in Cell Differentiation 46 Pages: 159-179
  • Peer Reviewed
• [Journal Article] Regulation of melanin-concentrating hormone receptor 1 signaling by RGS8 with the receptor third intracellular loop. (2008)
  • Author(s): Mayumi Miyamoto-Matsubara
  • Journal Title: Cellular Signaling 20 Pages: 2084-2094
  • Peer Reviewed
• [Journal Article] The pharmacological properties of a novel MCH1 receptor antagonist isolated from combinatorial libraries. (2008)
  • Author(s): Hiroshi Nagasaki
  • Journal Title: Eur J Pharmacol. 602 Pages: 194-202
  • Peer Reviewed
• [Journal Article] Signaling pathway of the goldfish melanin-concentrating hormone receptor 1 and 2.
  • Author(s): Hamamoto A, Mizusawa K, Takahashi A, Saito Y.
  • Journal Title: Regulatory Peptides. in press
  • Peer Reviewed
• [Presentation] MCHR1の一次繊毛局在に関わるアミノ酸残基の解析 (2011)
  • Author(s): 永田麻実, 斎藤祐見子
  • Organizer: 日本動物学会中国四国支部広島県例会
  • Place of Presentation: 広島
  • Year and Date: 2011-03-05
• [Presentation] 哺乳類MCHR1におけるGタンパク質選択機構の探索 (2011)
  • Author(s): 濱本明恵, 斎藤祐見子
  • Organizer: 日本動物学会中国四国支部広島県例会
  • Place of Presentation: 広島
  • Year and Date: 2011-03-05
• [Presentation] 哺乳類MCHR1におけるGタンパク質選択機構の探索 (2011)
  • Author(s): 濱本明恵
  • Organizer: 日本動物学会中国四国支部広島県例会
  • Place of Presentation: 東広島市
  • Year and Date: 2011-03-05
• [Presentation] MCHR1の一次繊毛局在に関わるアミノ酸残基の解析 (2011)
  • Author(s): 永田麻実
  • Organizer: 日本動物学会中国四国支部広島県例会
  • Place of Presentation: 東広島市
  • Year and Date: 2011-03-05
• [Presentation] メラニン凝集ホルモン受容体の多彩な機能 日本薬理学会主催-新薬理学セミナー (2010)
  • Author(s): 斎藤祐見子
  • Organizer: GPCRを基盤としたペプチド創薬の現状と展望
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-11-25
• [Presentation] メラニン凝集ホルモン受容体の多彩な機能 (2010)
  • Author(s): 斎藤祐見子
  • Organizer: 日本薬理学会主催-新薬理学セミナー「GPCRを基盤としたペプチド創薬の現状と展望
  • Place of Presentation: 鹿児島市(招待講演)
  • Year and Date: 2010-11-25
• [Presentation] キンギョメラニン凝集ホルモン受容体の機能解析 (2010)
  • Author(s): 濱本明恵, 水澤寛太, 高橋明義, 斎藤祐見子
  • Organizer: 第81回日本動物学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-23
• [Presentation] キンギョメラニン凝集ホルモン受容体の機能解析 (2010)
  • Author(s): 濱本明恵
  • Organizer: 第81回日本動物学会
  • Place of Presentation: 東京都
  • Year and Date: 2010-09-03
• [Presentation] Identification of amino acid involved in "gain-of-function" conformational dynamics of melanin-concentrating hormone receptor. (2010)
  • Author(s): Saito Y, Funakoshi Y, Saho T.
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] Identification of amino acid involved in "gain-of-function" conformational dynamics of melanin-concentrating hormone receptor. (2010)
  • Author(s): 斎藤祐見子
  • Organizer: Neuro2010
  • Place of Presentation: 神戸市
  • Year and Date: 2010-09-02
• [Presentation] 魚類メラニン凝集ホルモン受容体における情報伝達解析 (2010)
  • Author(s): 濱本明恵, 水澤寛太, 高橋明義, 斎藤祐見子
  • Organizer: 第7回GPCR研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-07
• [Presentation] 魚類メラニン凝集ホルモン受容体における情報伝達解析 (2010)
  • Author(s): 斎藤祐見子
  • Organizer: 第7回GPCR研究会
  • Place of Presentation: 東京都
  • Year and Date: 2010-05-07
• [Presentation] 脳内摂食受容体MCHR1の一次繊毛への局在化 (2010)
  • Author(s): 永田麻実, 斎藤祐見子
  • Organizer: 日本動物学会中国四国支部広島県例会
  • Place of Presentation: 広島
  • Year and Date: 2010-03-13
• [Presentation] キンギョMCH受容体における情報伝達系の解析 (2010)
  • Author(s): 濱本明恵, 水澤寛太, 高橋明義, 斎藤祐見子
  • Organizer: 日本動物学会中国四国支部広島県例会
  • Place of Presentation: 広島
  • Year and Date: 2010-03-13
• [Presentation] Recent advances for melanin-concentrating hormone and its receptors (2009)
  • Author(s): Miyamoto-Matsubara M, Chung S, Saito Y.
  • Organizer: Satellite symposium of the 9^<th> international symposium on VIP, PACAP, and related peptides
  • Place of Presentation: Yakushima, Japan
  • Year and Date: 2009-10-02
• [Presentation] Recent advances for melanin-concentrating hormone and its receptors (2009)
  • Author(s): Shinjae Chung
  • Organizer: Satellite symposium of the 9^<th> international symposium on VIP, PACAP, and related peptides
  • Place of Presentation: 鹿児島県熊毛郡屋久島町
  • Year and Date: 2009-10-02
• [Presentation] Selective RGS protein regulation of melanin-concentrating hormone receptor 1. (2009)
  • Author(s): 斎藤祐見子, 宮本真由美.
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬
  • Year and Date: 2009-06-24
• [Presentation] Selective RGS protein regulation of melanin-concentrating hormone receptor 1 (2009)
  • Author(s): 斎藤祐見子
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県渋川市伊香保町
  • Year and Date: 2009-06-22
• [Presentation] 摂食うつ不安に関連するGPCR(メラニン凝集ホルモン受容体)の構造活性相関と結合分子 (2008)
  • Author(s): 斎藤祐見子
  • Organizer: 第46回生物物理学会シンポジウム「GPCR型受容体を介した生物機能の物理的理解」
  • Place of Presentation: 福岡
  • Year and Date: 2008-12-04
• [Presentation] 摂食うつ不安に関連するGPCR(メラニン凝集ホルモン受容体)の構造活性相関と結合分子 (2008)
  • Author(s): 斎藤祐見子
  • Organizer: 第46回生物物理学会シンポジウム
  • Place of Presentation: 福岡市
  • Year and Date: 2008-12-04
• [Presentation] Regulation of the melanin-concentrating hormone receptor signaling by RGS (2008)
  • Author(s): Yumiko Saito
  • Organizer: 第52回北米神経科学会
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-19
• [Presentation] Regulation of the melanin concentrating hormone receptor signaling by RGS. (2008)
  • Author(s): Miyamoto-Matsubara M, Saitoh O, Saito Y
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington D.C. USA
  • Year and Date: 2008-11-18
• [Presentation] RGS modulates signaling of the melanin concentrating hormone receptor through the receptor third intracellular loop. (2008)
  • Author(s): 宮本真由美, 斎藤祐見子
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-13
• [Presentation] RGS modulates signaling of the melanin-concentrating hormone receptor through the receptor third intracellular loop (2008)
  • Author(s): 斎藤祐見子
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山市
  • Year and Date: 2008-09-13
• [Presentation] MCH 受容体におけるシグナリング調節分子の解析 (2008)
  • Author(s): 斎藤祐見子, 宮本真由美
  • Organizer: 第5回GPCR研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-09
• [Presentation] MCH受容体におけるシグナリング調節分子の解析 (2008)
  • Author(s): 斎藤祐見子
  • Organizer: 第5回GPCR研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-09
• [Presentation] 摂食GPCRの機能を調節する分子の同定 (2008)
  • Author(s): 宮本真由美, 斎藤祐見子
  • Organizer: Gシグナリング特定班合同若手ワークショップ(招待講演)
  • Place of Presentation: 箱根
  • Year and Date: 2008-01-26
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