Structural basis of LAMP2 aimed to modulate intracellular trafficking of lysosome

• Project/Area Number: 25463072
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Miki Yokoyama 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (70191533)
• Co-Investigator(Kenkyū-buntansha): KA 井上 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90302877)
• Co-Investigator(Renkei-kenkyūsha): SAKAMOTO Kensaku 独立行政法人理化学研究所, 拡張型遺伝暗号システム研究, チームリーダー (50240685) ; SHIROUZU Mikako 独立行政法人理化学研究所, 生命分子システム基盤研究領域, 上級研究員 (70280732)
• Research Collaborator: TERASAWA Kazue
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: リソソーム / LAMP-1 / LAMP-2 / アセンブリ / LAMP / 細胞内輸送 / ミトコンドリア / 骨芽細胞 / 骨細胞

Outline of Final Research Achievements

Lysosomes play a central role in the intracellular degradation. Lysosomes are also involved in the degradation of bone-matrix after fusion of lysosomes with plasma membranes. Lysosome-associated membrane proteins 1 and 2 (LAMP-1/2) are the most abundant protein components of lysosome membranes and suggested to be involved in the intracellular transport of lysosomes. However, the structural aspects of LAMPs have not been elucidated. In the present study, we demonstrated that (1) the subdomains of LAMP-1 and LAMP-2 adopt the unique β-prism fold, (2) the assembly modes of LAMP-1 and LAMP-2 are different.

Research Products

• [Journal Article] PDMP, a ceramide analogue, acts as an inhibitor of mTORC1 by inducing its translocation from lysosome to endoplasmic reticulum. (2017)
  • Author(s): Takashi O, Katarzyna A. Podyma-Inoue, Kazue T, Jin-ichi I, Toshihide K, Tetsuro W, Yuichi I, Miki Hara-Y.
  • Journal Title: Experimental Cell Research Volume: 350 Issue: 1 Pages: 103-114
  • DOI: 10.1016/j.yexcr.2016.11.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of Heparan Sulfate Proteoglycan-positive Recycling Endosomes Isolated from Glioma Cells. (2016)
  • Author(s): Podyma-Inoue KA, Moriwaki T, Rajapakshe AR, Terasawa K, Hara-Yokoyama M.
  • Journal Title: Cancer Genomics Proteomics. Volume: 13 Pages: 443-452
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lysosome-associated membrane proteins-1 and -2 (LAMP-1 and LAMP-2) assemble via distinct modes. (2016)
  • Author(s): Terasawa K, Tomabechi Y, Ikeda M, Ehara H, Kukimoto-Niino M, Wakiyama M, Podyma-Inoue KA, Rajapakshe AR, Watabe T, Shirouzu M, Hara-Yokoyama M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 479 Issue: 3 Pages: 489-495
  • DOI: 10.1016/j.bbrc.2016.09.093
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Preferential recognition of isocitrate dehydrogenase by a rabbit monoclonal antibody (ab124797) against the C-terminal peptide of RANKL (2015)
  • Author(s): Kazue Terasawa, Anupama R. Rajapakshe, Katarzyna A. Podyma-Inoue, Chiemi Mishima-Tsumagari, Masaki Yanagishita and Miki Hara-Yokoyama
  • Journal Title: Journal of Immunological Methods Volume: 420 Pages: 1-10
  • DOI: 10.1016/j.jim.2015.03.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lysosome-associated membrane proteins (LAMPs) regulate intracellular positioning of mitochondria in MC3T3-E1 cells (2015)
  • Author(s): Anupama R. Rajapakshe, Katarzyna A. Podyma-Inouea, Kazue Terasawa, Katsuya Hasegawa, Toshimitsu Namba, Yasuhiro Kumei, Masaki Yanagishita and Miki Hara-Yokoyama
  • Journal Title: EXPERIMENTAL CELL RESEARCH Volume: 331 Issue: 1 Pages: 211-222
  • DOI: 10.1016/j.yexcr.2014.09.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glycosylation Regulates CD38 Assembly on the Cell Surface (2013)
  • Author(s): Hara-Yokoyama, Miki
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 25 Issue: 146 Pages: 215-225
  • DOI: 10.4052/tigg.25.215
  • NAID: 130004841378
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Presentation] Heparan sulfate proteoglycan and intracellular transport; clues from proteomic analysis of transport vesicles (2015)
  • Author(s): Podyma-Inoue KA, Rajapakshe AR, Takuya Moriwaki, Teturo Watabe, and Miki Yokoyama
  • Organizer: BMB2015 第38回日本分子生物学会大会、第88回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県、神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Lysosome-associated membrane protein 1/2によるミトコンドリア細胞内輸送の制御 (2015)
  • Author(s): 横山 三紀
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県、新潟市）
  • Year and Date: 2015-09-11
• [Presentation] LAMP2 is invovled in the intracellular transport of RANKL (2013)
  • Author(s): Rajapakse Anupama, 井上 カタジナアンナ、柳下 正樹、横山 三紀
  • Organizer: 第５５回 歯科基礎医学会学術大会
  • Place of Presentation: 岡山コンベンションセンター