Unraveling of digital-like signal transduction systems in cell plasma membranes

• Project/Area Number: 15K14477
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Kyoto University
• Principal Investigator: SUZUKI KENICHI 京都大学, 物質－細胞統合システム拠点, 特定拠点准教授 (50423059)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: シグナル伝達 / 1分子観察 / ラフト / Src family kinase / Phospholipase C gamma / GPIアンカー型タンパク質 / EGF受容体 / PLCgamma / Grb2 / １分子観察

Outline of Final Research Achievements

We inspected a hypothesis that long analog-like signals by receptors in cell plasma membranes can be generated by summation of short digital-like signals. We performed single-molecule imaging of recruitment of signaling molecules to EGF receptors upon ligation, and found that the recruitment occurred for very short periods (less than 0.5 sec), but the frequency of the recruitment was increased as the bulk signal intensity was increased. These results strongly support the hypothesis.

Research Products

• [Int'l Joint Research] 国立生命科学研究センター(NCBS)/幹細胞・再生医学研究所(inStem)(インド)
• [Journal Article] Investigation of raft dynamics by single-molecule observation of ganglioside probes (2017)
  • Author(s): 鈴木健一
  • Journal Title: 生化学 Volume: 89 Issue: 1 Pages: 121-125
  • DOI: 10.14952/SEIKAGAKU.2017.890121
  • NAID: 40021119840
  • ISSN: 0037-1017
  • Year and Date: 2017-02-25
  • Peer Reviewed
• [Journal Article] Raft-based sphingomyelin interactions revealed by new fluorescent sphingomyelin analogs (2017)
  • Author(s): Masanao Kinoshita, Kenichi GN Suzuki, Nobuaki Matsumori, Misa Takada, Hikaru Ano, Kenichi Morigaki, Mitsuhiro Abe, Asami Makino, Toshihide Kobayashi, Koichiro M Hirosawa, Takahiro K Fujiwara, Akihiro Kusumi, Michio Murata
  • Journal Title: J Cell Biol Volume: 未定 Issue: 4 Pages: 1183-1204
  • DOI: 10.1083/jcb.201607086
  • NAID: 120005998045
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Raft-based interactions of gangliosides with a GPI-anchored receptor (2016)
  • Author(s): N. Komura, K. G. N. Suzuki, H. Ando, M. Konishi, M. Koikeda, A. Imamura, R. Chadda, T. K. Fujiwara, H. Tsuboi, R. Sheng, W. Cho, K. Furukawa, K. Furukawa, Y. Yamauchi, H. Ishida, A. Kusumi (Co-Corresponding Author), and M. Kiso
  • Journal Title: Nat. Chem. Biol. Volume: in press Issue: 6 Pages: 402-410
  • DOI: 10.1038/nchembio.2059
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane (2016)
  • Author(s): T. K. Fujiwara, Iwasawa, K., Kalay, Z., Tsunoyama, T. A. Y. Watanabe, Y. M. Umemura, H. Murakoshi, K. G. N. Suzuki, Y. L., Nemoto, N. Morone, A. Kusumi
  • Journal Title: Mol. Cell Biol. Volume: 27 Issue: 7 Pages: 1101-1119
  • DOI: 10.1091/mbc.e15-04-0186
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Single-molecule imaging of signal transduction via GPI-anchored receptors (2016)
  • Author(s): K. G. N. Suzuki
  • Journal Title: Methods Mol. Biol. Volume: 1376 Pages: 229-238
  • DOI: 10.1007/978-1-4939-3170-5_19
  • ISBN: 9781493931699, 9781493931705
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] New insights into the organization of the plasma membrane and its role in signal transduction (2015)
  • Author(s): Suzuki, K. G. N.
  • Journal Title: Int. Rev. Cell Mol. Biol. Volume: in press Pages: 67-96
  • DOI: 10.1016/bs.ircmb.2015.02.004
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 1分子観察によるガングリオシドのクラスター形成機構とEGF受容体活性制御機構の解明 (2017)
  • Author(s): 鈴木健一
  • Organizer: 新学術領域研究「神経糖鎖生物学」最終班会議
  • Place of Presentation: JPタワー名古屋
  • Year and Date: 2017-03-03
  • Invited
• [Presentation] 高精度1分子観察で初めて明らかになった細胞膜構造とシグナル伝達機構 (2017)
  • Author(s): 鈴木健一
  • Organizer: 第３回医薬獣連携研究会プログラム
  • Place of Presentation: 岐阜薬科大学
  • Year and Date: 2017-01-27
  • Invited
• [Presentation] Regulation mechanisms of EGF receptor activity by gangliosides as revealed by single-molecule imaging (2016)
  • Author(s): Kenichi G. N. Suzuki
  • Organizer: The 8th Asian Community for Glycoscience and Glycotechnology Annual Conference
  • Place of Presentation: Jiangnan University, Wuxi, China
  • Year and Date: 2016-10-13
  • Int'l Joint Research / Invited
• [Presentation] 1分子イメージングにより明らかになったガングリオシドの糖鎖相互作用によるEGF受容体活性制御機構 (2016)
  • Author(s): 鈴木健一
  • Organizer: 日本プロテオーム学会2016年大会
  • Place of Presentation: 北里大学
  • Year and Date: 2016-07-28
  • Invited
• [Presentation] Unraveling of raft organization and function by single-molecule imaging of new ganglioside probes (2016)
  • Author(s): Kenichi G. N. Suzuki
  • Organizer: The 21st iCeMS International Symposium
  • Place of Presentation: Kyoto University, Kyoto
  • Year and Date: 2016-06-03
  • Int'l Joint Research / Invited
• [Presentation] Raft organization and function revealed by single-molecule imaging of ganglioside probes (2016)
  • Author(s): K. G. N. Suzuki
  • Organizer: The 3rd International Symposium on Glyco-Neuroscience
  • Place of Presentation: 淡路国際会議場
  • Year and Date: 2016-01-14
  • Int'l Joint Research / Invited
• [Presentation] ガングリオシド糖鎖相互作用が誘起するラフトの組織化と機能の1分子観察による解明 (2015)
  • Author(s): 鈴木健一
  • Organizer: BMB2015
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Unraveling raft organization and function by GPI-anchored receptors and gangliosides (2015)
  • Author(s): K. G. N. Suzuki
  • Organizer: Super Resolution Seminar
  • Place of Presentation: inStem、バンガロール、インド
  • Year and Date: 2015-11-26
  • Int'l Joint Research / Invited
• [Presentation] 1分子イメージングにより明らかになったラフト組織化と機能のための最初のステップ (2015)
  • Author(s): 鈴木健一
  • Organizer: 日本顕微鏡学会第71回学術講演会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2015-05-13
  • Invited
• [Book] Glycoscience: Biology and Medicine (2015)
  • Author(s): K. G. N. Suzuki
  • Total Pages: 8
  • Publisher: Springer
• [Remarks] 脂質の挙動をありのままに再現する蛍光プローブでラフトの形成機構を解明
  • URL: http://www.icems.kyoto-u.ac.jp/ja/news/3598
• [Remarks] 新しい糖脂質蛍光プローブを開発して細胞膜の"筏ナノドメイン"を解明
  • URL: https://www.icems.kyoto-u.ac.jp/ja/news/2732
• [Remarks] 新しい糖脂質蛍光プローブを開発して細胞膜の"筏ナノドメイン"を解明
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2016/04/05-nr.html