Physiological substrates and functions of ABC proteins involved in lipid transport

• Project/Area Number: 20228001
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Applied biochemistry
• Research Institution: Kyoto University
• Principal Investigator: UEDA Kazumitsu 京都大学, 物質-細胞統合システム拠点, 教授 (10151789)
• Co-Investigator(Kenkyū-buntansha): AKATSU Hiroyasu 医療法人さわらび会福祉村病院, 長寿医学研究所, 副所長 (00399734) ; TODA Yoshinobu 天理医療大学, 医療学部, 准教授 (10444465)
• Co-Investigator(Renkei-kenkyūsha): KATO Hiroaki 京都大学, 大学院・薬学研究科, 教授 (90204487) ; UESUGI Motonari 京都大学, 物質-細胞統合システム拠点, 教授 (10402926) ; KUSUMI Akihiro 京都大学, 物質-細胞統合システム拠点, 教授 (50169992)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥161,070,000 (Direct Cost: ¥123,900,000、Indirect Cost: ¥37,170,000); Fiscal Year 2012: ¥31,720,000 (Direct Cost: ¥24,400,000、Indirect Cost: ¥7,320,000); Fiscal Year 2011: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000); Fiscal Year 2010: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000); Fiscal Year 2009: ¥33,540,000 (Direct Cost: ¥25,800,000、Indirect Cost: ¥7,740,000); Fiscal Year 2008: ¥29,770,000 (Direct Cost: ¥22,900,000、Indirect Cost: ¥6,870,000)
• Keywords: 動物生化学 / 膜輸送タンパク質 / ABC蛋白質 / 動脈硬化 / アルツハイマー病 / コレステロール / 膜タンパク質 / 神経疾患 / 生活習慣病 / 1分子イメージング / ABCタンパク質 / 善玉コレステロール / ケミカルライブラリー / iPS細胞 / ES細胞 / 1分子観察 / トランスポーター / 核内受容体 / 蛋白質相互作用 / ACBタンパク質 / アルツハイマー / タンパク質精製 / プロテアソーム / 遺伝病

Research Abstract

Many transporters in the protein family, ATP Binding Cassette (ABC) proteins, have been found to play important physiological roles through transporting lipids, and defects in their functions are related to various diseases. In this project, we tried to reveal theirphysiological substrates and functions by integrating biochemical/cell biological studies, single molecule tracking and crystal structure analyses.

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Research Products

• [Journal Article] 24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1. (2013)
  • Author(s): Matsuda, A., Nagao, K, Matsuo, M., Kioka N. and Ueda, K.
  • Journal Title: J. Neurochem. Volume: (in press) Issue: 1 Pages: 93-101
  • DOI: 10.1111/jnc.12275
  • Peer Reviewed
• [Journal Article] ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging. (2013)
  • Author(s): Nagata, K., O., Nakada, C.,, Kasai, R. S.,Kusumi, A. and Ueda, K.
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Issue: 13 Pages: 5034-5039
  • DOI: 10.1073/pnas.1220703110
  • Peer Reviewed
• [Journal Article] ATPase activity of human ABCG1 is stimulated by cholesterol and sphingomyelin. (2013)
  • Author(s): Hirayama, H., Kimura, Y., Kioka, N., Matsuo,M. and Ueda, K.
  • Journal Title: J. Lipid Res. Volume: 54 Issue: 2 Pages: 496-502
  • DOI: 10.1194/jlr.m033209
  • Peer Reviewed
• [Journal Article] ATPase activity of nucleotide binding domains of human MDR3 in the context of MDR1 (2013)
  • Author(s): Ishigami, M.. Tominaga, Y., Nagao, K., Kimura, Y., Matsuo, M., Kioka, N. and Ueda, K
  • Journal Title: Biochim Biophys Acta-MCBL Volume: 1831 Issue: 4 Pages: 683-690
  • DOI: 10.1016/j.bbalip.2012.12.016
  • Peer Reviewed
• [Journal Article] Cyclosporine A and PSC833 inhibit ABCA1 function via direct binding. (2013)
  • Author(s): Nagao, K., Maeda, M., Manucat, M. B., and Ueda, K.
  • Journal Title: Biochim Biophys Acta-MCBL Volume: 1831 Issue: 2 Pages: 398-406
  • DOI: 10.1016/j.bbalip.2012.11.002
  • Peer Reviewed
• [Journal Article] ATP hydrolysis-dependent conformational changes in the extracellular domain of ABCA1 are associated with apoA-I binding. (2012)
  • Author(s): Nagao, K., Takahashi, K., Azuma, Y., Takada, M., Kimura, Y., Matsuo, M., Kioka, N. and Ueda, K.
  • Journal Title: J Lipid Res Volume: 53 Issue: 1 Pages: 126-136
  • DOI: 10.1194/jlr.m019976
  • Peer Reviewed
• [Journal Article] Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex. (2012)
  • Author(s): Hulpke, S, Tomioka, M, Kremmer, E, Ueda, K, Abele, R, Tampe, R
  • Journal Title: Cell Mol Life Sci. Volume: 69 Issue: 19 Pages: 317-3327
  • DOI: 10.1007/s00018-012-1005-6
  • Peer Reviewed
• [Journal Article] Lysine residues of ABCA1 are required for the interaction with apoA-I (2012)
  • Author(s): Nagao, K.
  • Journal Title: Biochin Biophys Ada Volume: 1,821 Issue: 3 Pages: 530-535
  • DOI: 10.1016/j.bbalip.2011.06.024
  • Peer Reviewed
• [Journal Article] LXRβ directly interacts with ABCA1 to promote HDL formation during acute cholesterol accumulation (2011)
  • Author(s): Hozoji-Inada, M., Munehira, Y., Nagao, K., Kioka, N., and Ueda, K.
  • Journal Title: J Biol Chem. Volume: 286 Issue: 22 Pages: 20117-24
  • DOI: 10.1074/jbc.m111.235846
  • Peer Reviewed
• [Journal Article] WAVE2 forms a complex with cAMP-dependent protein kinase (PKA) and is involved in PKA enhanceient of membrane protrusions (2011)
  • Author(s): Yamashita, H.
  • Journal Title: J Biol Chem. Volume: 286 Issue: 5 Pages: 3907-3914
  • DOI: 10.1074/jbc.m110.145409
  • Peer Reviewed
• [Journal Article] Function and regulation of ABCA1-Membrane meso-domain organization and re-organizationprotrusions (2011)
  • Author(s): Nagao, K.
  • Journal Title: FEBS J. Volume: 278 Issue: 18 Pages: 3190-3203
  • DOI: 10.1111/j.1742-4658.2011.08170.x
  • Peer Reviewed
• [Journal Article] ABC Proteins Protect the Human Body and Maintain Optimal Health (2011)
  • Author(s): Ueda, K.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 75 Issue: 3 Pages: 401-409
  • DOI: 10.1271/bbb.100816
  • NAID: 10028201102
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] LXRβ directlyinteracts with ABCA1 to promote HDLformation during acute cholesterolaccumulation (2011)
  • Author(s): Hozoji-Inada, M., Munehira, Y., Nagao,K., Kioka, N., Ueda, K.
  • Journal Title: J Biol Chem 印刷中
  • Peer Reviewed
• [Journal Article] LXRβ directly interacts with ABCA1 to promote HDL formation during acute cholesterol accumulation (2011)
  • Author(s): Hozoji-Inada, M.
  • Journal Title: J Biol Chem Volume: 286 Pages: 20117-24
  • Peer Reviewed
• [Journal Article] Involvement of low-density lipoprotein receptor-related protein and ABCG1 in stimulation of axonal extension by apoE-containing lipoproteins (2011)
  • Author(s): Matsuo, M.
  • Journal Title: Biochim Biophys Acta Volume: 1811 Pages: 31-38
  • Peer Reviewed
• [Journal Article] Lipid outward translocation by ABC proteins (2010)
  • Author(s): Nagao, K.
  • Journal Title: FEBS Lett Volume: 21 Pages: 451-456
  • Peer Reviewed
• [Journal Article] Formation of two intramolecular disulfide bonds is necessary for apoA-I-dependent cholesterol efflux mediated by ABCA1. (2009)
  • Author(s): Hozoji, M., Kimura, Y., Kioka, N., and Ueda, K.
  • Journal Title: J Biol Chem. Volume: 284 Issue: 17 Pages: 11293-11300
  • DOI: 10.1074/jbc.m900580200
  • Peer Reviewed
• [Journal Article] Sodium taurocholate-dependent lipid efflux by ABCA1-Effects of W590Smutation on lipid translocation and apoA-I dissociation. (2009)
  • Author(s): Nagao, K. Zhao, Y., Takahashi, K., Kimura, Y., and Ueda, K.
  • Journal Title: J Lipid Res Volume: 50 Issue: 6 Pages: 1165-1172
  • DOI: 10.1194/jlr.m800597-jlr200
  • Peer Reviewed
• [Journal Article] Formation of two intra moleculardisulfide bonds is necessary forapoA-I-dependent cholesterol effluxmediated by ABCA1 (2009)
  • Author(s): Hozoji, M., Kimura, Y., Kioka, N., Ueda, K.
  • Journal Title: J. Biol. Chem 284 Pages: 11293-11300
  • Peer Reviewed
• [Journal Article] Sodium taurocholate-dependent lipid efflux byABCA1-Effects of W590S mutation on lipidtranslocation and apoA-I dissociation. (2009)
  • Author(s): Nagao, K. Zhao, Y., Takahashi, K.,Kimura, Y., Ueda, K.
  • Journal Title: J.Lipid Res. 50 Pages: 1165-1172
  • Peer Reviewed
• [Journal Article] The retroendocytosis pathway of ABCA1/apoA-Icontributes to HDL formation. (2009)
  • Author(s): Azuma, Y., Takada, M., Shin, H-W.,Kioka, N., Nakayama, K., Ueda, K.
  • Journal Title: Genes Cells 14 Pages: 191-204
  • Peer Reviewed
• [Journal Article] Formation of two intramolecular disulfide bonds is necessary for apoA-I-dependent cholesterol efflux mediated by ABCA1. (2009)
  • Author(s): Hozoji, M.
  • Journal Title: J Biol Chem. 284 Pages: 11293-11300
  • Peer Reviewed
• [Journal Article] Sodium taurocholate-dependent lipid efflux by ABCA1-Effects of W590S mutation on lipid translocation and apoA-I dissociation. (2009)
  • Author(s): Nagao, K.
  • Journal Title: J.Lipid Res. 50 Pages: 1165-1172
  • Peer Reviewed
• [Journal Article] Improved expression and purification of human multidrug resistance protein MDR1 from baculovirus-infected insect cells. (2009)
  • Author(s): Kodan, A.
  • Journal Title: Protein Expr.Purif. 66 Pages: 7-14
  • Peer Reviewed
• [Journal Article] The retroendocytosis pathway of ABCA1/apoA-I contributes to HDL formation (2009)
  • Author(s): Azuma, Y.
  • Journal Title: Genes to Cells 14 Pages: 191-204
  • Peer Reviewed
• [Journal Article] A Novel Missense Mutation of ABCA1 in Transmembrane・-Helix in a Japanese Patient with Tangier Disease. (2009)
  • Author(s): Maekawa, M.
  • Journal Title: Atherosclerosis 206 Pages: 216-222
  • Peer Reviewed
• [Journal Article] Functional role of the linker region in purified human P-glycoprotein. (2009)
  • Author(s): Sato, T.
  • Journal Title: FEBS J. 276 Pages: 3504-16
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of subcellular localization of ABCG5 and ABCG8 (2009)
  • Author(s): 208.Hirata, T
  • Journal Title: Biosci Biotechnol Biochem. 73 Pages: 619-626
  • Peer Reviewed
• [Journal Article] The retroendocytosis pathway of ABCA1/apoA-I contributesto HDL formation. (2009)
  • Author(s): Azuma, Y
  • Journal Title: Genes to Cells 14 Pages: 191-204
  • Peer Reviewed
• [Journal Article] Sodium taurocholate-dependent lipid efflux by ABCA1-Effects of W590S mutation on lipid translocation and apoA-I dissociation. (2009)
  • Author(s): Nagao, K.
  • Journal Title: J. Lipid Res. 50 Pages: 1165-1172
  • Peer Reviewed
• [Journal Article] Direct interaction of nuclear receptor LXRβ with ABCA1 modulates cholesterol efflux. (2008)
  • Author(s): Hozoji, M, Munehira, Y, Ikeda, Y, Makishima,M, Matsuo, M, Kioka, N, Ueda, K
  • Journal Title: J Biol Chem. Volume: 283 Issue: 44 Pages: 30057-30063
  • DOI: 10.1074/jbc.m804599200
  • Peer Reviewed
• [Journal Article] Direct interaction of nuclearreceptor LXRβ with ABCA1 modulatescholesterol efflux. (2008)
  • Author(s): Hozoji, M., Munehira, Y., Ikeda, Y.,Makishima, M., Matsuo, M., Kioka, N.,Ueda, K.
  • Journal Title: J.Biol.Chem 283 Pages: 30057-30063
  • Peer Reviewed
• [Journal Article] The ABCA1 Q597R mutant undergoes trafficking from the ER upon ER stress. (2008)
  • Author(s): Tanaka AR
  • Journal Title: Biochem Biophys Res Commun. 369 Pages: 1174-1178
  • Peer Reviewed
• [Journal Article] Formation of cholesterol-enriched structures by aberrant intracellular accumulation of ATP-binding cassette (2008)
  • Author(s): Tanaka AR
  • Journal Title: Genes to Cells 13 Pages: 889-904
  • Peer Reviewed
• [Journal Article] Direct interaction of nuclear receptor LXRbeta with ABCA1 modulates cholesterol efflux. (2008)
  • Author(s): Hozoji M
  • Journal Title: J Biol Chem. 283 Pages: 30057-30063
  • Peer Reviewed
• [Presentation] Mechanismof the generation of HDL, membrane meso particles, by ABCA1 (2013)
  • Author(s): 植田和光
  • Organizer: The 14th International Membrane Research Forum
  • Place of Presentation: 京都大学
  • Invited
• [Presentation] Mechanism of ABCA1-mediated HDL formation. (2012)
  • Author(s): Ueda, K.
  • Organizer: 5th SFB symposium: Transmembrane Transporters in Health and Disease
  • Place of Presentation: Austria
  • Year and Date: 2012-09-24
• [Presentation] Mechanism of HDL formation by ABCA1. (2012)
  • Author(s): Ueda, K. Nagao, K. Nagata, K.
  • Organizer: ASBMB: Frontiers in Lipid Biology .
  • Place of Presentation: Canada
  • Year and Date: 2012-09-22
• [Presentation] Mechanism of cholesterol efflux by ABCA1. (2012)
  • Author(s): Ueda, K. Nagao, K. Nagata, K.
  • Organizer: FASEB Meeting: New Frontiers in Transport ATPases
  • Place of Presentation: USA
  • Year and Date: 2012-06-05
• [Presentation] Mechanism of function and regulation of ABCA1 in HDL formation. (2012)
  • Author(s): Ueda, K.
  • Organizer: CLS (Peking Univ)-iCeMS (Kyoto Univ) Joint symposium
  • Place of Presentation: China
  • Year and Date: 2012-04-21
• [Presentation] Mechanism of function and regulation of ABCA1 in HDL formation (2012)
  • Author(s): 植田和光
  • Organizer: CLS (Peking Univ)-iCeMS (Kyoto Univ) Joint symposium
  • Place of Presentation: 北京大学（中国）
  • Invited
• [Presentation] Mechanism of cholesterol efflux by ABCA1 (2012)
  • Author(s): 植田和光
  • Organizer: FASEB Meeting: New Frontiers in Transport ATPases
  • Place of Presentation: コロラド（アメリカ）
  • Invited
• [Presentation] Crystal structure of a MDR1-type ABC protein (2012)
  • Author(s): 植田和光
  • Organizer: 第71回日本癌学会学術総会シンポジウム
  • Place of Presentation: ホテルロイトン札幌
  • Invited
• [Presentation] Mechanism of ABCA1-mediated HDL formation (2012)
  • Author(s): 植田和光
  • Organizer: 5th SFB symposium: Transmembrane Transporters in Health and Disease
  • Place of Presentation: ウイーン大学（オーストリア）
  • Invited
• [Presentation] 動脈硬化予防の鍵を握るABCA1 (2012)
  • Author(s): 植田和光
  • Organizer: 第85回日本生化学会大会シンポジウム
  • Place of Presentation: 福岡国際会議場
  • Invited
• [Presentation] 健康をまもる ABC タンパク質-ビタミンとトランスポーター (2011)
  • Author(s): 植田和光
  • Organizer: 鈴木梅太郎先生ビタミンB1発見100周年祝典・記念シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-11-25
• [Presentation] 核内受容体LXRbetaは細胞膜上のABCA1と直接結合しHDL形成を制御する (2011)
  • Author(s): Kazumitsu Ueda
  • Organizer: ABC2011 in Kyoto・ABC Proteins/Membrane Meso-domains/ES-iPS cells
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-11-17
• [Presentation] The nuclear receptor LXRbeta directly interacts with ABCA1 to promote HDL formation during acute cholesterol accumulation (2011)
  • Author(s): 植田和光
  • Organizer: 第84回日本生化学会大会シンポジウム
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] The nuclear receptor LXRbeta directly interacts with ABCA1 to promote HDL formation during acute cholesterol accumulation (2011)
  • Author(s): Kazumitsu Ueda
  • Organizer: Gordon Research Conference, Molecular & Cellular Biology of Lipids
  • Place of Presentation: 米国,ニューハンプシャー(招待講演)
  • Year and Date: 2011-07-20
• [Presentation] The nuclear receptor LXRβ directly interacts with ABCA1 to promote HDL formation during acute cholesterol accumulation. (2011)
  • Author(s): Ueda, K.
  • Organizer: Gordon Reseach Conferences on Molecular & Cellular Biology of Lipids
  • Place of Presentation: USA
  • Year and Date: 2011-07-19
• [Presentation] Mechanism and regulation of HDL formation by ABCA1. (2010)
  • Author(s): Ueda, K.
  • Organizer: The 3rd SFB symposium:Transmembrane Transporters in Health and Disease.
  • Place of Presentation: Austria
  • Year and Date: 2010-09-04
• [Presentation] Mechanism and regulation ofHDL formation by ABCA1. (2010)
  • Author(s): Ueda, K.
  • Organizer: The 3rd SFBsymposium "Transmembrane Transportersin Health and Disease"
  • Place of Presentation: Vienna, Austria 招待講演
  • Year and Date: 2010-09-04
• [Presentation] A novel post-translationalregulation of ABCA1 for HDL formation inacute cholesterol accumulation. (2010)
  • Author(s): Ueda, K.
  • Organizer: 6th IASSponsoredWorkshop on High DensityLipoproteins
  • Place of Presentation: Whistler, Canada招待講演
  • Year and Date: 2010-05-19
• [Presentation] A novel post-translational regulation of ABCA1 (2010)
  • Author(s): Kazumitsu Ueda
  • Organizer: The 6th International Atherosclerosis Society
  • Place of Presentation: カナダ,バンクーバー(招待講演)
  • Year and Date: 2010-05-19
• [Presentation] Mechanism and regulation ofHDL formation by ABCA1. (2010)
  • Author(s): Ueda, K.
  • Organizer: 3rd FEBSSpecial Meeting "ABC Proteins"
  • Place of Presentation: Innsbruck, Austria, 招待講演
  • Year and Date: 2010-03-03
• [Presentation] Mechanism and regulation of HDL formation by ABCA1 (2010)
  • Author(s): Ueda, K.
  • Organizer: 3rd FEBS Special Meeting "ABC Proteins : from multidrug resistance to genetic diseases"
  • Place of Presentation: Innsbruck, Austria
  • Year and Date: 2010-03-03
• [Presentation] ABCA1 : Mechanisms andregulations of HDL formation. (2009)
  • Author(s): Ueda, K.
  • Organizer: 5th TakedaScience Foundation Symposium onPharmaSciences "Bioactive LipidMolecules and Transporters"
  • Place of Presentation: Tokyo,招待講演
  • Year and Date: 2009-05-25
• [Presentation] ABCA1 : Mechanisms and regulations of HDL formation (2009)
  • Author(s): Ueda, K.
  • Organizer: 第5回武田科学振興財団薬科学シンポジウム"Bioactive lipid molecules and Transporters"
  • Place of Presentation: 東京, Grand Prince Hotel Takanawa
  • Year and Date: 2009-05-25
• [Presentation] ヒト培養細胞を用いたヒトABCトランスポーターの大量発現系の構築および精製条件スクリーニング手法の開発 (2008)
  • Author(s): 木村泰久
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] Biological function of ABC transporters and its relation to lipid metabolism (2008)
  • Author(s): 植田和光
  • Organizer: 第40回日本動脈硬化学会
  • Place of Presentation: つくば
  • Year and Date: 2008-07-10
• [Presentation] ABC蛋白質の基質認識メカニズムと活性制御 (2008)
  • Author(s): 植田和光
  • Organizer: 第8回日本蛋白質科学会年会
  • Place of Presentation: 東京・舟橋
  • Year and Date: 2008-06-10
• [Presentation] 健康をまもるトランスポーター”ABC 蛋白質”
  • Author(s): 植田和光
  • Organizer: 岐阜大学創立６３周年記念講演会
  • Place of Presentation: 岐阜大学
  • Invited
• [Book] The ABC transporters of human physiology and disease. (2011)
  • Author(s): Nagao, K. Hozoji-Inada, M. Azuma, Y. and Ueda, K
  • Publisher: World Scientific
• [Book] The ABC transporters of humanphysiology and disease(ABCA1-Mediated HDLFormation : Mechanism and Regulation in)(ed by Linton, K., Holland, IB)
  • Author(s): Nagao, K., Hozoji-Inada, M., Azuma, Y., Ueda, K.
  • Publisher: World ScientificPublishing Co 印刷中
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• [Remarks] 受賞平成22年度日本農芸化学会賞受賞ホームページ
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