Investigation of the Vps10p-family proteins and its sorting disorders in life-style-related diseases

• Project/Area Number: 25293074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: Kanzaki Makoto 東北大学, 医工学研究科, 准教授 (10272262)
• Co-Investigator(Renkei-kenkyūsha): HATAKEYAMA HIROYASHU 東北大学, 学際科学フロンティア研究所, 助教 (00619067)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 生活習慣病 / ソーティング障害 / インスリン反応性 / 糖尿病 / 骨格筋 / ソーティング / 小胞輸送 / GLUT4 / インスリン / インスリン抵抗性 / 細胞内小胞輸送系 / 脂肪細胞 / マイオカイン / アディポカイン

Outline of Final Research Achievements

Physiological relevance of the Tripartite Complex Assembly composed of Vps10p/soluble ligands/GLUT4 was revealed by several experimental approaches including the single-molecule imaging analysis. Live-imaging analysis allowed us to visualize the transient formation of tripartite complex in a living cell and this approach successfully demonstrated that intracellular dynamics of the tripartite complex containing GLUT4 is tightly regulated by Tbc1d-family RabGAPs (AS160 and Tbc1d1).

Research Products

• [Int'l Joint Research] Laval University Medical Center(Canada)
• [Int'l Joint Research] Francis Crick Institute(英国)
• [Int'l Joint Research] Aarhus University(Denmark)
• [Int'l Joint Research] Leibniz Center, Medicine & Biosciences(Germany)
• [Journal Article] アミロイド前駆タンパク質の新規プロセシング経路の発見 (2016)
  • Author(s): 神崎 展
  • Journal Title: 実験医学 Volume: 34(1) Pages: 66-67
• [Journal Article] 電気パルスを用いた収縮型培養骨格筋細胞の創製 (2016)
  • Author(s): 神崎 展
  • Journal Title: 機会の研究 Volume: 68(1) Pages: 56-58
• [Journal Article] Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis. (2015)
  • Author(s): Chiba K, Tsuchiya M, Koide M, Hagiwara Y, Sasaki K, Hattori Y, Watanabe M, Sugawara S, Kanzaki M, Endo Y.
  • Journal Title: PLoS One Volume: 10 (11):e0143635 Issue: 11 Pages: e0143635-e0143635
  • DOI: 10.1371/journal.pone.0143635
  • Peer Reviewed / Open Access
• [Journal Article] Improvement of Cell Membrane Permeability Using a Cell-Solution Electrode for Generating Atmospheric-Pressure Plasma (2015)
  • Author(s): T. Kaneko, S. Sasaki, Y. Hokari, S. Horiuchi, R. Honda, and M. Kanzaki
  • Journal Title: Biointerphases Volume: 10 Issue: 2 Pages: 029521-029521
  • DOI: 10.1116/1.4921278
  • Peer Reviewed / Open Access
• [Journal Article] 脂質ラフト形成において細胞膜内外が共役するしくみ (2015)
  • Author(s): 神崎 展
  • Journal Title: 実験医学 Volume: 33(11) Pages: 1759-1760
• [Journal Article] ゴルジ複合体における輸送小胞の選択的な繋留とその意義 (2015)
  • Author(s): 神崎 展
  • Journal Title: 実験医学1月号（2015） Volume: 33（1） Pages: 57-58
• [Journal Article] Insulin-Mimicking Bioactivities of Acylated Inositol Glycans in Several Mouse Models of Diabetes with or without Obesity. (2014)
  • Author(s): 5.Suzuki S, Suzuki C, Hinokio Y, Ishigaki Y, Katagiri H, Kanzaki M, Azev VN, Chakraborty N, d'Alarcao M.
  • Journal Title: PLoS One. Volume: 9 Issue: 6 Pages: e100466-e100466
  • DOI: 10.1371/journal.pone.0100466
  • Peer Reviewed / Open Access
• [Journal Article] Highly Efficient and Minimally Invasive Transfection Using Time-Controlled Irradiation of Atmospheric-Pressure Plasma (2014)
  • Author(s): S. Sasaki, M. Kanzaki, and T. Kaneko
  • Journal Title: Applied Physics Express Volume: 7 Issue: 2 Pages: 026202-026202
  • DOI: 10.7567/apex.7.026202
  • NAID: 210000136990
  • Peer Reviewed
• [Journal Article] Hydrogel-based bioassay sheets for in vitro evaluation of contraction-dependent metabolic regulation in skeletal muscle cells (2014)
  • Author(s): Kuniaki Nagamine, Kohei Okamoto, Shingo Otani, Hirokazu Kaji, Makoto Kanzaki, Matsuhiko Nishizawa
  • Journal Title: Biomater. Sci. Volume: 2 Issue: 2 Pages: 252-256
  • DOI: 10.1039/c3bm60179j
  • Peer Reviewed
• [Journal Article] 細胞容量調節の「鍵」チャネルSWELL1の同定 (2014)
  • Author(s): 神崎 展
  • Journal Title: 実験医学7月号（2014） Volume: 32（11） Pages: 1750-1751
• [Journal Article] Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells (2014)
  • Author(s): Rutti S, Arous C, Nica AC, Kanzaki M, Halban PA, Bouzakri K.
  • Journal Title: FEBS Lett. Volume: 588(1) Issue: 1 Pages: 15-20
  • DOI: 10.1016/j.febslet.2013.10.050
  • Peer Reviewed
• [Journal Article] 微小管アセチル化とエンドサイトーシスが細胞進路を決める (2014)
  • Author(s): 神崎 展
  • Journal Title: 実験医学 Volume: 32(1) Pages: 65-66
• [Journal Article] Development of dual-color simultaneous single molecule imaging system for analyzing multiple intracellular trafficking activities (2013)
  • Author(s): Hatakeyama H, Kanzaki M.
  • Journal Title: Conf Proc IEEE Eng Med Biol Soc. Volume: 2013 Pages: 1418-1421
  • DOI: 10.1109/embc.2013.6609776
  • Peer Reviewed
• [Journal Article] Single quantum dot tracking reveals that an individual multivalent 2 HIV-1 Tat-protein transduction domain can activate machinery for 3 lateral transport and endocytosis (2013)
  • Author(s): 3.Yasuhiro Suzuki*, Chandra Nath Roy, Warunya Promjunyaku, Hiroyasu Hatakeyama, Kohsuke Gonda, Junji Imamura, Biju Vasudevan Pillai, Noriaki Ohuchi, Makoto Kanzaki , Hideo Higuchi, and Mitsuo Kaku
  • Journal Title: Mol. Cell Biol. Volume: 33 Issue: 15 Pages: 3039-3049
  • DOI: 10.1128/mcb.01717-12
  • Peer Reviewed / Open Access
• [Journal Article] 細胞融合にかかわるアクチン制御ナノシステムとその可視化解析 (2013)
  • Author(s): 神崎 展
  • Journal Title: 実験医学 Volume: 31(11) Pages: 1749-1750
• [Presentation] The Human Satellite Cells can Form the Myotube Even in the Atrophic Fatty Muscle of Rotator Cuff Tear (2016)
  • Author(s): Koide M, Hagiwara Y, Ando A, Yabe Y, Kanazawa K, Sekiguchi T, Itaya N, Yoshida S, Itoi E, Kanzaki M, Hatakeyama H, Tsuchiya M
  • Organizer: Orthopaedic Research Society 2016 Annual Meeting
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] マウス走行運動モデルと電気パルス強収縮モデルを用いた収縮骨格筋の生物学的応答の解析―GLUT4制御に関わる分子基盤について― (2016)
  • Author(s): 細谷 雅浩、堰合 茂智、畠山 裕康、神崎 展
  • Organizer: 第4回骨格筋生物学研究会
  • Place of Presentation: 松本大学，長野
  • Year and Date: 2016-03-04
• [Presentation] Roles of exercise-induced gene, SPARC, against sarcopenia: link between extracellular matrix and mitochondria. (2015)
  • Author(s): Malouane A, Carbonell A, Yoshioka M, Kanzaki M, Puymirat J, St-Amand J:
  • Organizer: 8th Cachexia Conference
  • Place of Presentation: Paris, France
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] Cellular Nanoscience and Exercise-induced Health Benefits (2015)
  • Author(s): Kanzaki M, Hatakeyama H
  • Organizer: International Conference on Fluid Dynamics 2015 “Advanced Physical Stimuli and Biological Responses”
  • Place of Presentation: Sendai, International Center
  • Year and Date: 2015-10-28
  • Int'l Joint Research / Invited
• [Presentation] AS160 vs Tbc1d1: Cooperative determination of insulin-responsive GLUT4 trafficking activity after exercise-mimetic stimuli (2015)
  • Author(s): Hatakeyama H, Kanzaki M
  • Organizer: 51st Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2015-09-14
  • Int'l Joint Research
• [Presentation] AS160 and Tbc1d1 as a determinant of insulin sensitivity in GLUT4 trafficking (2015)
  • Author(s): Hatakeyama H, Kanzaki M
  • Organizer: FASEB SRC "Glucose Transport: Gateway to Metabolic Systems Biology"
  • Place of Presentation: Big Sky, MT, USA
  • Year and Date: 2015-07-26
  • Int'l Joint Research
• [Presentation] Involvement of Mechanosensitive Transcriptional Network in Contraction-dependent Muscle Fiber Type Conversion Analyzed using the "in vitro Exercise Model" (2015)
  • Author(s): Hosoya M, Uda Y, Hatakeyama H, Kanzaki M
  • Organizer: Cell Symposia "Exercise Metabolism"
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2015-07-12
  • Int'l Joint Research
• [Presentation] 生細胞内における単一分子レベルの視覚化解析と分子動態生理学の創造 (2015)
  • Author(s): 神崎 展
  • Organizer: 日本動物細胞工学会2015年大会
  • Place of Presentation: 仙台・片平さくらホール
  • Year and Date: 2015-07-09
  • Invited
• [Presentation] In vitro Exercise モデルを用いた骨格筋の運動効果発現機序の探索 (2015)
  • Author(s): 神崎 展
  • Organizer: 第3回骨格筋生物学研究会
  • Place of Presentation: 仙台・東北大学星陵キャンパス
  • Year and Date: 2015-03-07 – 2015-03-09
• [Presentation] GLUT4一分子挙動計測に基づくTBC/RabGAPsが司る運動効果の分子基盤解析 (2015)
  • Author(s): 畠山裕康，神崎 展
  • Organizer: 第3回骨格筋生物学研究会
  • Place of Presentation: 仙台・東北大学星陵キャンパス
  • Year and Date: 2015-03-07 – 2015-03-09
• [Presentation] 運動依存性GLUT4トランスロケーション機構の解析―電気パルス刺激によるマウス骨格筋の強収縮モデルを用いた試み (2015)
  • Author(s): 細谷雅浩・畠山裕康・土谷昌広・神崎 展
  • Organizer: 第3回骨格筋生物学研究会
  • Place of Presentation: 仙台・東北大学星陵キャンパス
  • Year and Date: 2015-03-07 – 2015-03-09
• [Presentation] Quantum-dot-based Nanometrological Analysis of Intracellular Trafficking Activities in Living Cell (2015)
  • Author(s): Makoto Kanzaki
  • Organizer: The Joint Symposium of 9th International Symposium on Medical, Bio- and Nano-Electronics, and 6th International Workshop on Nanostructures & Nanoelectronics.
  • Place of Presentation: Sendai, Katahira Capmus
  • Year and Date: 2015-03-02 – 2015-03-04
• [Presentation] インスリン感受性と筋の運動効果 (2014)
  • Author(s): 神崎 展
  • Organizer: 第46回徳島大学糖尿病臨床・研究センター講演会
  • Place of Presentation: 徳島，徳島大学
  • Year and Date: 2014-11-11
  • Invited
• [Presentation] Submissive Role of AS160 in Tbc1d1-mediated GLUT4 Trafficking Activation in Response to Ca2+ and Insulin (2014)
  • Author(s): Hiroyasu Hatakeyama, Makoto Kanzaki
  • Organizer: 74th American Diabetes Association Scientific Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-06-16 – 2014-06-18
• [Presentation] 筋の運動効果とインスリン感受性の亢進 (2014)
  • Author(s): 神崎 展
  • Organizer: 第26回バイオエンジニアリング講演会
  • Place of Presentation: 東北大学片平キャンパス, 仙台
  • Invited
• [Presentation] Muscle Contractile Activity and its Beneficial Effects in Type 2 Diabetes (2013)
  • Author(s): Makoto Kanzaki
  • Organizer: 10th International Conference on Flow Dynamics
  • Place of Presentation: Sendai International Center, Sendai
  • Invited
• [Presentation] Comprehensive viewing of intracellular trafficking activities based on single molecule imaging (2013)
  • Author(s): Hatakeyama H. and Kanzaki M
  • Organizer: 2013 Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: The New Orleans Ernest N. Morial Convention Center, USA
• [Presentation] Establishment of intracellular trafficking nanometry in single isolated myofibers (2013)
  • Author(s): Kaita S., Shinagawa R., Hatakeyama H. and Kanzaki M.
  • Organizer: 2013 Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: The New Orleans Ernest N. Morial Convention Center, USA
• [Presentation] Free Fatty Acids and Exercise Effects on Muscle Fiber Type Conversion Revealed by the “in Vitro Exercise Model” (2013)
  • Author(s): Uda, Y., Nakagaito, Y., Fuse, H., Mori, M., and Kanzaki, M.
  • Organizer: 2013 Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: The New Orleans Ernest N. Morial Convention Center, USA
• [Presentation] Intracellular trafficking nanometry for quantifying GLUT4 translocation (2013)
  • Author(s): Hatakeyama H. and Kanzaki M.
  • Organizer: FASEB Science Research Conferences
  • Place of Presentation: Snowmass Village, CO, USA
• [Presentation] Development of dual-color simultaneous single molecule imaging system for analyzing multiple intracellular trafficking activities (2013)
  • Author(s): Hatakeyama H. and Kanzaki M.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
  • Place of Presentation: Osaka International Convention Center, Osaka
• [Presentation] Molecular basis of Tbc1d1 for acquiring temporal insulin-responsive ability triggering GLUT4 translocation (2013)
  • Author(s): Hatakeyama H. and Kanzaki M.
  • Organizer: 73rd Scientific Session of the American Diabetes Association
  • Place of Presentation: Chicago, USA
• [Presentation] Tbc1d1が示すインスリン不応性およびインスリン応答性GLUT4輸送制御とその遷移による「インスリン応答性獲得」の分子基盤 (2013)
  • Author(s): 畠山 裕康, 神崎 展
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本、熊本
• [Remarks] 神崎研究室HP
  • URL: http://www.ecei.tohoku.ac.jp/kanzaki/index.html
• [Remarks] Research Gate, Makoto Kanzaki HP
  • URL: https://www.researchgate.net/profile/Makoto_Kanzaki/
• [Remarks] Research Gate HP
  • URL: https://www.researchgate.net/profile/Makoto_Kanzaki/
• [Remarks] Research Gate
  • URL: https://www.researchgate.net/profile/Makoto_Kanzaki/
• [Remarks] 神崎研ホームページ
  • URL: http://www.ecei.tohoku.ac.jp/kanzaki/index.html