Analysis of regulatory mechanisms of cell surface expression of G protein-coupled receptor signaling complex

• Project/Area Number: 21200007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology; Living organism molecular science
• Research Institution: Tohoku University
• Principal Investigator: SUKEGAWA Jun 東北大学, 大学院・医学系研究科, 准教授 (30187687)
• Co-Investigator(Kenkyū-buntansha): SATO Takeya 東北大学, 大学院・医学系研究科, 助教 (10312696) ; KURAMASU Atsuo 山口大学, 大学院・医学系研究科, 准教授 (90302091) ; SAITO Masaki 秋田大学, 大学院・医学系研究科, 助教 (50400271)
• Co-Investigator(Renkei-kenkyūsha): YANAGISAWA Teruyuki 東北大学, 大学院・医学系研究科, 教授 (90133941)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥30,160,000 (Direct Cost: ¥23,200,000、Indirect Cost: ¥6,960,000); Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000); Fiscal Year 2010: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000); Fiscal Year 2009: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 神経伝達物質・受容体 / 活性発現の分子機構 / 受容体細胞表面発現 / 受容体 / 細胞内輸送 / 細胞表面発現 / シグナル複合体

Research Abstract

G protein-coupled receptors (GPCRs) have been well known as molecular targets for many clinically important drugs. In order to function properly at cell surface, the receptors have to be transported efficiently as receptor-signaling molecule complexes to the cell surface after the GPCRs are synthesized at ribosomes. This research identified several cellular proteins that interact with carboxy-termini of GPCRs and showed that these interacting proteins regulate the transport and the cell surface expression of the cognate GPCRs.

Research Products

• [Journal Article] Cell Fate Control Gene Therapy Based on Engineered Variants of Human Deoxycytidine Kinase (2012)
  • Author(s): Sato T
  • Journal Title: Molecular Therapy Volume: 20 Issue: 5 Pages: 1002-1013
  • DOI: 10.1038/mt.2011.298
  • Peer Reviewed
• [Journal Article] Preparation of photo-cross-linked small molecule affinity matrices for affinity selection of protein targets for biologically active small molecules (2012)
  • Author(s): Moriya T
  • Journal Title: Methods in Molecular Biology Volume: 800 Pages: 75-83
  • DOI: 10.1007/978-1-61779-349-3_6
  • ISBN: 9781617793486, 9781617793493
  • Peer Reviewed
• [Journal Article] Expression of anti-HVEM single-chain antibody on tumor cells induces tumor-specific immunity with long-term memory (2012)
  • Author(s): Kuramasu A
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 61 Issue: 2 Pages: 203-214
  • DOI: 10.1007/s00262-011-1101-8
  • Peer Reviewed
• [Journal Article] The hydrophobic amino acids in putative helix 8 in carboxy-terminus of histamine H(3) receptor are involved in receptor-G-protein coupling (2011)
  • Author(s): Kuramasu A, Sukegawa J, Sato T, Sakurai E, Watanabe T, Yanagisawa T, Yanai K
  • Journal Title: Cellular Signalling Volume: 23 Pages: 1843-1849
  • Peer Reviewed
• [Journal Article] Detection of cytochrome P450 substrates by using a small-molecule droplet array on an NADH-immobilized solid surface (2011)
  • Author(s): Moriya T
  • Journal Title: Chembiochem Volume: 12 Issue: 18 Pages: 2748-2752
  • DOI: 10.1002/cbic.201100541
  • Peer Reviewed
• [Journal Article] Functional interaction between purinergic receptors : effect of ligands for A2A and P2Y12 receptors on P2Y1 receptor function (2011)
  • Author(s): Moriya T
  • Journal Title: FEBS Letter Volume: 585 Issue: 24 Pages: 3978-3984
  • DOI: 10.1016/j.febslet.2011.10.050
  • Peer Reviewed
• [Journal Article] Distinctive effects of arachidonic acid and docosahexaenoic acid on neural stem/progenitor cells (2011)
  • Author(s): Moriya T
  • Journal Title: Genes to Cells Volume: 16 Issue: 7 Pages: 778-790
  • DOI: 10.1111/j.1365-2443.2011.01527.x
  • Peer Reviewed
• [Journal Article] Herpesvirus entry mediator regulates hypoxia-inducible factor-1α and erythropoiesis in mice (2011)
  • Author(s): Kuramasu A
  • Journal Title: Journal of Clinical Investigation Volume: 121 Issue: 12 Pages: 4810-4819
  • DOI: 10.1172/jci57332
  • Peer Reviewed
• [Journal Article] Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons (2010)
  • Author(s): Sukegawa J
  • Journal Title: Neuroscience Research Volume: 67 Pages: 126-136
  • Peer Reviewed
• [Journal Article] Evidence for the involvement of Lfc and Tctex-1 in axon formation (2010)
  • Author(s): Saito M
  • Journal Title: Journal of Neuroscience Volume: 30 Pages: 6793-6800
  • Peer Reviewed
• [Journal Article] Roles of hypothalamic subgroup histamine and orexin neurons on behavioral responses to sleep deprivation induced by the treadmill method in adolescent rats (2010)
  • Author(s): Kuramasu A
  • Journal Title: Journal of Pharmacological Sciences Volume: 114 Pages: 444-453
  • Peer Reviewed
• [Journal Article] B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance (2010)
  • Author(s): Kuramasu A
  • Journal Title: Blood Volume: 116 Pages: 1291-1298
  • Peer Reviewed
• [Journal Article] Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons (2010)
  • Author(s): Sanda M
  • Journal Title: Neuroscience Research (In presss, 未定)
  • Peer Reviewed
• [Journal Article] Involvement of aquaporin in thromboxane A2 receptor-mediated, G12/13/RhoA/NHE-sensitive cell swelling in 1321N1 human astrocytoma cells (2010)
  • Author(s): Saito M
  • Journal Title: Cell Signal 22 Pages: 41-46
  • Peer Reviewed
• [Journal Article] Multiple histamine receptor gene knockout mice and their phenotypes. (2009)
  • Author(s): Sakurai E, Kuramasu A, Watanabe T, Yanai K.
  • Journal Title: Inflammation Research 58 Volume: suppl 1 Pages: 41-42
  • Peer Reviewed
• [Journal Article] Thromboxane A2 receptor-mediated epidermal growth factor receptor transactivation : involvement of PKC-delta and PKC-epsilon in the shedding of epidermal growth factor receptor ligands (2009)
  • Author(s): Uchiyama K
  • Journal Title: Eur J Pharm Sci 38 Pages: 504-511
  • Peer Reviewed
• [Journal Article] Inhibitory effects of Atractylodis lanceae rhizoma and Poria on collagen-or thromboxane A2-induced aggregation in rabbit platelets (2009)
  • Author(s): Nasu Y
  • Journal Title: Biol Pharm Bull 32 Pages: 856-860
  • Peer Reviewed
• [Journal Article] Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity (2009)
  • Author(s): Omiya R
  • Journal Title: Immunology 128 Pages: 543-555
  • Peer Reviewed
• [Journal Article] Multiple histamine receptor gene knockout mice and their phenotypes (2009)
  • Author(s): Sakurai E
  • Journal Title: Inflamm Res 58, suppl 1 Pages: 41-42
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor broadens lentivector distribution in the heart after neonatal injection (2009)
  • Author(s): Sato T
  • Journal Title: J Cardiol 54 Pages: 245-254
  • NAID: 10025583300
  • Peer Reviewed
• [Presentation] 加齢による肝臓時計の同調障害にはアドレナリンα1受容体シグナル低下が関与する (2012)
  • Author(s): 守屋孝洋
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-16
• [Presentation] ヒスタミンH3受容体結合タンパク質の受容体結合コンセンサス配列の解析 (2012)
  • Author(s): 助川 淳、佐藤岳哉、柳澤輝行
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] PICK1とGHRHRの相互作用は、GHRHRの細胞表面発現を制御する (2012)
  • Author(s): 佐藤岳哉、助川 淳、柳澤輝行
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] ヒスタミンH4受容体を介するケモタキシスにおける低分子量Gタンパク質Racの関与 (2012)
  • Author(s): 倉増敦朗
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] ヒスタミンH4受容体を介するケモタキシスにおける低分子量Gタンパク質Racの関与 (2011)
  • Author(s): 倉増敦朗
  • Organizer: 第64回日本薬理学会西南部会
  • Place of Presentation: 博多
  • Year and Date: 2011-11-20
• [Presentation] Gタンパク質共役型受容体細胞内トラフィッキング制御タンパク質の解析 (2011)
  • Author(s): 助川 淳
  • Organizer: 新薬理学セミナー2011
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-30
• [Presentation] AZT誘発心筋ミトコンドリア機能障害は、酸化ストレスによるものである (2011)
  • Author(s): 佐藤岳哉
  • Organizer: 第62回日本薬理学会北部会
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-30
• [Presentation] トロンボキサンA2受容体シグナルにおける脂質ラフトの役割 (2011)
  • Author(s): 守屋孝洋
  • Organizer: 第62回日本薬理学会北部会
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-29
• [Presentation] 加齢による肝臓時計同調障害におけるアドレナリンα1受容体シグナル低下の関与 (2011)
  • Author(s): 守屋孝洋
  • Organizer: 第62回日本薬理学会北部会
  • Place of Presentation: 仙台
  • Year and Date: 2011-09-29
• [Presentation] GHRHRの Carboxy末端に結合するPICK1は、受容体の細胞表面発現を調節する (2011)
  • Author(s): 佐藤岳哉、助川 淳、柳澤輝行
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-23
• [Presentation] GHRHRのCarboxy末端に結合するPICK1は、受容体の細胞表面発現を調節する (2011)
  • Author(s): 佐藤岳哉
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-23
• [Presentation] 種間で保存されたCCR4-NOT複合体による新しい心機能調節機構 (2011)
  • Author(s): 斎藤将樹
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-23
• [Presentation] Tctex-1のリン酸化を介した一次線毛の短縮機序の解明 (2011)
  • Author(s): 斎藤将樹
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-22
• [Presentation] リピドミクスによる炎症終息脂質メディエーターのインフルエンザ重症化における役割の検討 (2011)
  • Author(s): 斎藤将樹
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-22
• [Presentation] DRiP78 interacts with the carboxy-terminus of histamine H3 receptor and decreases the expression of the receptor (2010)
  • Author(s): 助川 淳、佐藤岳哉、柳澤輝行
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] DRiP78 interacts with the carboxy-terminus of histamine H3receptor and decreases the expression of the receptor (2010)
  • Author(s): 助川淳
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] 抗ガン治療法としてのTmpk/AZT系におけるBystander効果発現の分子機構 (2010)
  • Author(s): 佐藤岳哉
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] マウス線維芽細胞におけるセラミド刺激によるNGF産生機構の解明 (2010)
  • Author(s): 斎藤将樹
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] ヒスタミンH3受容体に結合する細胞内タンパク質の機能解析 (2010)
  • Author(s): 助川 淳、佐藤岳哉、柳澤輝行
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-18
• [Presentation] 新生マウスに対するVEGF前投与は遺伝子治療効果を改善する (2010)
  • Author(s): 佐藤岳哉
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-18
• [Presentation] 副甲状腺ホルモン受容体機能に及ぼすTctex-1の役割の解明 (2010)
  • Author(s): 斎藤将樹、助川 淳、柳澤輝行
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] 拘束及び心理的ストレスに対するヒスタミン受容体の役割:遺伝子ノックアウトマウスを用いた研究 (2010)
  • Author(s): 及川綾子
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] ヒスタミンH3受容体の細胞内トラフィッキング制御因子の解析 (2009)
  • Author(s): 助川 淳
  • Organizer: 第37回薬物活性シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-10-09
• [Presentation] トロンボキサンA2受容体における糖鎖修飾の生理的意義の解明 (2009)
  • Author(s): 斎藤将樹
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] トロンボキサンA2受容体を介したシグナル伝達に対する脂質ラフトの関与 (2009)
  • Author(s): 斎藤将樹
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] 副甲状腺ホルモン受容体機能に及ぼすTctex-1の役割の解明 (2009)
  • Author(s): 斎藤将樹、柳澤輝行、助川 淳
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] ヒスタミンH3受容体に結合する細胞内タンパク質の機能解析 (2009)
  • Author(s): 助川 淳、佐藤岳哉、柳澤輝行
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] ヒスダミンH3受容体に結合する細胞内タンパク質の機能解析 (2009)
  • Author(s): 木下和樹
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] 新規自殺遺伝子治療法 tmpk/AZT系の抗ガン治療法としての有用性の検証(In vivo Bystander 効果の確認) (2009)
  • Author(s): 佐藤岳哉
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] Gap junction-mediated bystander killing highlights the utility of the TmpkF105Y/AZT system for cancer suicide gene therapy (2009)
  • Author(s): 佐藤岳哉
  • Organizer: 第15回日本遺伝子治療学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-11
• [Presentation] Cell surface expression of histamine H3 receptor is regulated by proteins interacting with the carboxy terminus of the receptor (2009)
  • Author(s): 助川 淳、佐藤岳哉、柳澤輝行
  • Organizer: 10th International Symposium on Mechanisms of Vasodilation (MOVD2009)
  • Place of Presentation: 宮城県松島
  • Year and Date: 2009-06-03
• [Presentation] Cell surface expression of histamine H3 receptor is regulated by proteins interacting with the carboxy-terminus of the receptor (2009)
  • Author(s): 木下和樹
  • Organizer: 10th International Symposium on Mechanisms of Vasodilation (MOVD2009)
  • Place of Presentation: 宮城県松島
  • Year and Date: 2009-06-03