Physiological substrates and functions of ABC proteins involved in lipid transport

2012 Fiscal Year Final Research Report

• 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
• Keywords: 動物生化学 / 膜輸送タンパク質

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.

Research Products

• [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 Pages: 5034-5039
  • DOI: 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 Pages: 496-502
  • DOI: 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 Pages: 683-690
  • DOI: doi:10.1016/j.bbalip.2012.12.016oi: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 Pages: 398-406
  • DOI: 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 Pages: 126-136
  • DOI: 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 Pages: 317-3327
  • DOI: doi:10.1007/s00018-012-1005-6
  • 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 Pages: 20117-24
  • DOI: doi:10.1074/jbc.M111.235846
  • 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 Pages: 11293-11300
  • DOI: 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 Pages: 1165-1172
  • DOI: doi:10.1194/jlr.M800597-JLR200
  • 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 Pages: 30057-30063
  • DOI: doi:10.1074/jbc.M804599200
  • Peer Reviewed
• [Journal Article] 24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1.
  • Author(s): Matsuda, A., Nagao, K, Matsuo, M., Kioka N. and Ueda, K.
  • Journal Title: J. Neurochem. Volume: (in press)
  • DOI: doi:10.1111/jnc.12275
  • Peer Reviewed
• [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] 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] 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
• [Book] The ABC transporters of human physiology and disease. (2011)
  • Author(s): Nagao, K. Hozoji-Inada, M. Azuma, Y. and Ueda, K
  • Total Pages: 29-51
  • Publisher: World Scientific
• [Remarks] ホームページ
  • URL: http://www.biochemistry.kais.kyoto-u.ac.jp/