Molecular mechanisms and functions of structural changes of protein GPI-anchors

2013 Fiscal Year Final Research Report

• Project/Area Number: 21247018
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: KINOSHITA Taroh 大阪大学, 微生物病研究所, 教授 (10153165)
• Co-Investigator(Kenkyū-buntansha): MAEDA Yusuke 大阪大学, 微生物病研究所, 准教授 (00294124) ; MURAKAMI Yoshiko 大阪大学, 微生物病研究所, 准教授 (00304048) ; MORITA Yasuhiro 大阪大学, 微生物病研究所, 助教 (70397769) ; FUJITA Morihisa 大阪大学, 微生物病研究所, 助教 (30532056)
• Project Period (FY): 2009-04-01 – 2014-03-31
• Keywords: GPIアンカー / 遺伝子 / 酵素 / タンパク質 / 糖鎖

Research Abstract

GPI-anchor is a glycolipid acts as a membrane anchor of many eukaryotic cell surface proteins. In this study, we aimed to clarify (1) mechanisms and biological significance of fatty acid remodeling of GPI-anchored proteins (GPI-AP); (2) mechanism and biological significance of 1-alkyl, 2-acyl form of GPI anchors; and (3) roles of GPI structural remodeling in transport of GPI-AP. We found (1) that GPI fatty acid remodeling is important for homeostasis of humoral immunity; (2) that 1-alkyl, 2-acyl form of GPI anchors is defective in major peroxisome disorders; and (3) that proper remodeling of GPI-AP is critical for association with their cargo receptors and efficient transport.

Research Products

• [Journal Article] Significance of GPI-anchored protein enrichment in lipid rafts for the control of autoimmunity (2013)
  • Author(s): Wang, Y., Y. Murakami, T. Yasui, S. Wakana, H. Kikutani, T. Kinoshita and Y. Maeda
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 25490-25499
  • DOI: 10.1074/jbc.M113.492611
  • Peer Reviewed
• [Journal Article] A case of paroxysmal nocturnal hemoglobinuria (PNH) caused by a germline mutation and a somatic mutation in PIGT (2013)
  • Author(s): Krawitz, P. M., B. Hochsmann, Y. Murakami, B. Teubner, U. Kruger, E. Klopocki, H. Neitzel, A. Hollein, D. Parkhomchuk, J. Hecht, P. N. Robinson, S. Mundlos, T. Kinoshita and H. Schrezenmeier
  • Journal Title: Blood Volume: 122 Pages: 1312-1315
  • DOI: 10.1182/blood-2013-01-481499
  • Peer Reviewed
• [Journal Article] Glycosylphosphatidylinositol mannosyltransferase II is the rate-limiting enzyme in glycosylphosphatidylinositol biosynthesis under limited dolichol-phosphate mannose availability (2013)
  • Author(s): Hirata, T., M. Fujita, N. Kanzawa, Y. Murakami, Y. Maeda and T. Kinoshita
  • Journal Title: J. Bio chem Volume: 154 Pages: 257-264
  • DOI: 10.1093/jb/mvt045
  • Peer Reviewed
• [Journal Article] Transport of glycosylphosphatidylinositol-anchored proteins from the endoplasmic reticulum (2013)
  • Author(s): Kinoshita, T., Y. Maeda and M. Fujita
  • Journal Title: Biochim. Biophys. Acta - Mol. Cell Res Volume: 1833 Pages: 2473-2478
  • DOI: 10.1016/j.bbamcr.2013.01.027
  • Peer Reviewed
• [Journal Article] GPI anchors regulate glycosphingolipid levels (2012)
  • Author(s): Loizides-Mangold, U., F. P. A. David, V. J. Nesatyy, T. Kinoshita and H. Riezman
  • Journal Title: J. Lipid Res Volume: 53 Pages: 1522-1534
  • DOI: 10.1194/jlr.M025692
  • Peer Reviewed
• [Journal Article] Mutations in PIGO, a member of the GPI anchor synthesis pathway, cause hyperphosphatasia with mental retardation (2012)
  • Author(s): Krawitz, P. M., Y. Murakami, J. Hecht, U. Kruger, S. E. Holder, G. R. Mortier, B. delle Chiaie, M. D. Thompson, T. Roscioli, S. Kielbasa, T. Kinoshita, S. Mundlos, P. N. Robinson and D. Horn
  • Journal Title: Am. J. Hum. Genet Volume: 91 Pages: 146-151
  • DOI: 10.1016/j.ajhg.2012.05.004
  • Peer Reviewed
• [Journal Article] Enhanced response of T lymphocytes from Pgap3 knockout mouse : Insight into roles of fatty acid remodeling of GPI anchored proteins (2012)
  • Author(s): Murakami, H., Y. Wang, H. Hasuwa, Y. Maeda, T. Kinoshita and Y. Murakami
  • Journal Title: Biochem. Biophys. Res. Comm Volume: 417 Pages: 1235-1241
  • DOI: 10.1016/j.bbrc.2011.12.116
  • Peer Reviewed
• [Journal Article] GPI-anchor remodeling : potential functions of GPI-anchors in intracellular trafficking and membrane dynamics (2012)
  • Author(s): Fujita, M. and T. Kinoshita
  • Journal Title: Biochim. Biophys. Acta - Mol. Cell Biol. Lipids Volume: 1821 Pages: 1050-1058
  • DOI: 10.1016/j.bbalip.2012.01.004
  • Peer Reviewed
• [Journal Article] Defective lipid remodeling of GPI anchors in peroxisomal disorders, Zellweger syndrome, and rhizomelic chondrodysplasia punctata (2012)
  • Author(s): Kanzawa, N., N. Shimozawa, R. J. A. Wanders, K. Ikeda, Y. Murakami, H. R. Waterham, S. Mukai, M. Fujita, Y. Maeda, R. Taguchi, Y. Fujiki and T. Kinoshita
  • Journal Title: J. Lipid Res Volume: 53 Pages: 653-663
  • DOI: 10.1194/jlr.M021204
  • Peer Reviewed
• [Journal Article] Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia-mental retardation syndrome (2012)
  • Author(s): Murakami, Y., N. Kanzawa, K. Saito, P. M. Krawitz, S. Mundlos, P. N. Robinson, A. Karadimitris, Y. Maeda and T. Kinoshita
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 6318-6325
  • DOI: 10.1074/jbc.M111.331090
  • Peer Reviewed
• [Journal Article] Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria (2012)
  • Author(s): Murakami, Y., N. Inoue, T. Shichishima, R. Ohta, H. Noji, Y. Maeda, J. Nishimura, Y. Kanakura and T. Kinoshita
  • Journal Title: Br. J. Haematol Volume: 156 Pages: 383-387
  • DOI: 10.1111/j.1365-2141.2011.08914.x
  • Peer Reviewed
• [Journal Article] Sorting of GPI-anchored proteins into ER-exit sites by p24 proteins is dependent on remodeled GPI (2011)
  • Author(s): Fujita, M., R. Watanabe, N. Jaensch, M. Romanova-Michaelides, T. Satoh, M. Kato, H. Riezman, Y. Yamaguchi, Y. Maeda and T. Kinoshita
  • Journal Title: J. Cell Biol Volume: 194 Pages: 61-75
  • DOI: 10.1083/jcb.201012074
  • Peer Reviewed
• [Journal Article] Structural remodeling, trafficking and functions of glycosylphosphatidylinositol anchored proteins (2011)
  • Author(s): Maeda, Y. and T. Kinoshita
  • Journal Title: Prog. Lipid Res Volume: 50 Pages: 411-422
  • DOI: 10.1016/j.plipres.2011.05.002
  • Peer Reviewed
• [Journal Article] The acidic environment of the Golgi is critical for glycosylation and transport (2010)
  • Author(s): Maeda, Y. and T. Kinoshita
  • Journal Title: Methods Enzymol Volume: 480 Pages: 495-510
  • DOI: 10.1016/S0076-6879(10)80022-9
  • Peer Reviewed
• [Journal Article] Biogenesis of GPI-anchored proteins is essential for surface expression of sodium channels in zebrafish Rohon-Beard neurons to respond to mechanosensory stimulation (2010)
  • Author(s): Nakano, Y., M. Fujita, K. Ogino, T. Kinoshita, Y. Oda and H. Hirata
  • Journal Title: Development Volume: 137 Pages: 1689-1698
  • DOI: 10.1242/dev.047464
  • Peer Reviewed
• [Journal Article] Structural remodeling of GPI anchors during biosynthesis and after attachment to proteins (2010)
  • Author(s): Fujita, M. and T. Kinoshita
  • Journal Title: FEBS Lett Volume: 584 Pages: 1670-1677
  • DOI: 10.1016/j.febslet.2009.10.079
  • Peer Reviewed
• [Journal Article] Controlled expression of branch-forming mannosyltransferase is critical for mycobacterial lipoarabinomannan biosynthesis (2010)
  • Author(s): Sena, C. B., T. Fukuda, K. Miyanagi, S. Matsumoto, K. Kobayashi, Y. Murakami, Y. Maeda, T. Kinoshita and Y. S. Morita
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 13326-13336
  • DOI: 10.1074/jbc.M109.077297
  • Peer Reviewed
• [Journal Article] Peroxisome dependency of alkyl-containing GPI-anchor biosynthesis in the endoplasmic reticulum (2009)
  • Author(s): Kanzawa, N., Y. Maeda, H. Ogiso, Y. Murakami, R. Taguchi, and T. Kinoshita
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 106 Pages: 17711-17716
  • DOI: 10.1073/pnas.0904762106
  • Peer Reviewed
• [Journal Article] GPI-glycan remodeling by PGAP5 regulates transport of GPI-anchored proteins from the ER to the Golgi (2009)
  • Author(s): Fujita, M., Y. Maeda, M. Ra, Y. Yamaguchi, R. Taguchi and T. Kinoshita
  • Journal Title: Cell Volume: 139 Pages: 352-365
  • DOI: 10.1016/j.cell.2009.08.040
  • Peer Reviewed
• [Presentation] Structural Changes of GPI Anchor after its Attachment to Proteins : Functional Significance (2014)
  • Author(s): Taroh Kinoshita
  • Organizer: IUBMB 10^<th> International Symposium on Biochemical Roles of Eukaryotic Cell Surface Macromolecules
  • Place of Presentation: Kolkata, India
  • Year and Date: 2014-01-24
• [Presentation] タンパク質への付加後に起こるGPI アンカーの構造変化の機能的意義 (2013)
  • Author(s): 木下タロウ, 前田裕輔, 藤田盛久
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会館 他
  • Year and Date: 2013-12-04
• [Presentation] Remodeling and function of GPI anchors in protein sorting, trafficking, and dynamics (2013)
  • Author(s): Taroh Kinoshita
  • Organizer: FASEB Science Research Conferences : Protein Lipidation, Signaling, and Membrane Domrins
  • Place of Presentation: Saxtons River, Vermont, USA
  • Year and Date: 2013-07-15
• [Presentation] GPI アンカー型タンパク質の切断に関与する新規酵素の機能解析 (2012)
  • Author(s): 藤田盛久, 李 健熺, 村上良子, 前田裕 輔, 木下タロウ
  • Organizer: 第31回日本糖質学会年会
  • Place of Presentation: 鹿児島市民文化ホール
  • Year and Date: 20120917-20
• [Presentation] GPI アンカー型タンパク質の輸送とアンカー切断に関わる膜ドメイン -- Transport and anchor-cleavage of GPI-ancired proteins in relation to membrane domains (2012)
  • Author(s): 木下タロウ, 前田裕輔, 藤田盛久
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場 他
  • Year and Date: 2012-12-11
• [Presentation] Screening patients with inherited GPI anchor deficiency to establish concept of the new disease (2012)
  • Author(s): Yoshiko Murakami, Norimitsu Inoue, Yusuke Maeda, Yukitoshi Takahashi, Taroh Kinoshita
  • Organizer: XXIV International Complement Workshop
  • Place of Presentation: クレタ島 ギリシャ
  • Year and Date: 2012-10-12
• [Presentation] Deficiencies of GPI mannosyltransferases 1 and 2 cause different fates of GPI anchored proteins (2012)
  • Author(s): Taroh Kinoshita
  • Organizer: GlycoT 2012 Hannover
  • Place of Presentation: Hannover Germany
  • Year and Date: 2012-06-07
• [Presentation] Remodeling of GPI anchors in the ER before and after attachment to proteins : mechanisms and functions. (2011)
  • Author(s): Taroh Kinoshita
  • Organizer: Glyco 21(21th International Symposium on Glyconjugates)
  • Place of Presentation: ウィーン, オーストリア
  • Year and Date: 2011-08-23
• [Presentation] Remodeling of GPI-ancherd protein during biosynthesis in and transport from the ER, Towards a comprehensive understanding of endoplasmic reticulum functions (2010)
  • Author(s): Taroh Kinoshita
  • Organizer: EMBO Conference series
  • Place of Presentation: Girona Spain
  • Year and Date: 2010-10-04
• [Presentation] The pathogenesis of PNH (2010)
  • Author(s): Taroh Kinoshita
  • Organizer: The Second Session of Blood Diseases, Forum of Institute of Hematology & Hospital of Blood Diseases CAMs & PUMC
  • Place of Presentation: Tianjin China
  • Year and Date: 2010-05-06
• [Presentation] GPI-glycan remodeling by PGAP5 regulates transport of GPI-anchored proteins from the ER to the Golgi (2009)
  • Author(s): Taroh Kinoshita, Yusuke Maeda, Moonjin Ra, Yoshiki Yamaguchi, Ryo Taguti, Morihisa Fujita
  • Organizer: 20^<th> International Symposium on Glycoconjugates
  • Place of Presentation: San Juan, Perto Rico, USA
  • Year and Date: 2009-12-03
• [Book] Overview of GPI biosynthesis. In The Enzymes, Vol. 26 (2009)
  • Author(s): Taroh Kinoshita, M. Fujita, Eds. Menon, A. K., Kinoshita, T., Orlean, P., Tamanoi, F
  • Total Pages: 1-30
  • Publisher: Academic Press
• [Remarks] ホームページ
  • URL: http://www.biken.osaka-u.ac.jp/biken/men-eki-huzen/index.html