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Understanding the role of the endoplasmic reticulum - plasma membrane contact sites in lipid transport

Research Project

Project/Area Number 17H05065
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKumamoto University

Principal Investigator

Saheki Yasunori  熊本大学, 生命資源研究・支援センター, 客員准教授 (30794458)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2019: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2018: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords脂質 / 膜接着部位 / 小胞体 / 細胞膜 / extendedシナプトタグミン / GRAMD1タンパク質 / コレステロール / GRAMD1 / リソソーム / 脂質輸送タンパク質 / extended シナプトタグミン / Ca2+ / 神経科学 / 細胞・組織 / ゲノム
Outline of Final Research Achievements

The endoplasmic reticulum (ER), where the majority of membrane lipids are synthesized, extends throughout the cell and forms physical contacts with virtually all other cellular organelles, including the plasma membrane. Growing evidence suggests that lipid transfer proteins (LTPs) act at membrane contact sites and transport specific lipids from one membrane to another independent of membrane traffic. However, the molecular mechanisms that regulate the functions of LTPs are still largely elusive. In this study, we investigate how the functions of LTPs are regulated, focusing on ER-plasma membrane contact sites. Defects in cellular lipid homeostasis are linked to numerous human disorders, including neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease. Thus, our research not only provides insight into fundamental cell biology but also paves a way toward developing a novel therapeutic approach against neurodegeneration.

Academic Significance and Societal Importance of the Research Achievements

我々の体は無数の細胞から形成されている。各々の細胞は、脂質を主成分とする細胞膜で包まれているが、いかにして細胞膜の脂質組成が保たれているかはよくわかっていない。本研究を通して、細胞内での脂質輸送の分子機構がより一層明らかになり、細胞膜脂質の維持機構に関して知見を深めることができた。細胞内での脂質分布の異常は、様々な病態を引き起こすことが知られている。特に、神経細胞における生体膜の脂質組成の破綻は、アルツハイマー病やパーキンソン病などの神経変性疾患の要因となることが示唆されている。それゆえ、本研究は、将来的にこれら疾患の更なる病態解明および新規治療法の発見につながると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report

Research Products

(25 results)

All 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 11 results) Remarks (2 results)

  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] National University of Singapore(シンガポール)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Yale University(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] National University of Singapore(Singapore)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex2019

    • Author(s)
      Naito Tomoki、Ercan Bilge、Krshnan Logesvaran、Triebl Alexander、Koh Dylan Hong Zheng、Wei Fan-Yan、Tomizawa Kazuhito、Torta Federico Tesio、Wenk Markus R、Saheki Yasunori
    • Journal Title

      Elife

      Volume: 8

    • DOI

      10.7554/elife.51401

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Meeting Report From the 2019 “Organelle Zone” Symposium in Osaka, Japan2019

    • Author(s)
      Levine Tim P.、Perez Franck、Saheki Yasunori、von Blume Julia
    • Journal Title

      Contact

      Volume: 2

    • DOI

      10.1177/2515256419877091

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SMP domain proteins in membrane lipid dynamics2019

    • Author(s)
      Jeyasimman Darshini、Saheki Yasunori
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 19 Pages: 1388-1388

    • DOI

      10.1016/j.bbalip.2019.04.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca2+ releases E‐Syt1 autoinhibition to couple ER‐plasma membrane tethering with lipid transport2017

    • Author(s)
      Bian Xin、Saheki Yasunori、De Camilli Pietro
    • Journal Title

      The EMBO Journal

      Volume: 37 Pages: 219-234

    • DOI

      10.15252/embj.201797359

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Endoplasmic Reticulum - Plasma Membrane Crosstalk Mediated by the Extended Synaptotagmins2017

    • Author(s)
      Saheki Yasunori
    • Journal Title

      Organelle Contact Sites. Advances in Experimental Medicine and Biology

      Volume: 997 Pages: 83-93

    • DOI

      10.1007/978-981-10-4567-7_6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Extended-Synaptotagmins2017

    • Author(s)
      Saheki Yasunori、De Camilli Pietro
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1864 Pages: 1490-1493

    • DOI

      10.1016/j.bbamcr.2017.03.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Endoplasmic Reticulum - Plasma Membrane Contact Sites2017

    • Author(s)
      Saheki Yasunori、De Camilli Pietro
    • Journal Title

      Annual Review of Biochemistry

      Volume: 86 Pages: 659-684

    • DOI

      10.1146/annurev-biochem-061516-044932

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The regulation of plasma membrane cholesterol states via GRAMD1 lipid transfer protein complex2019

    • Author(s)
      Yasunori Saheki
    • Organizer
      ASCB|EMBO 2019 meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional dissection of membrane contact sites in intracellular lipid transport2019

    • Author(s)
      Yasunori Saheki
    • Organizer
      The 42nd Annual Meeting of the Molecular Biology Society of Japan, Fukuoka, Japan
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Cross-talk between the endoplasmic reticulum and the plasma membrane mediated by the extended synaptotagmins2019

    • Author(s)
      Yasunori Saheki
    • Organizer
      NEURO2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Functional dissection of membrane contact sites in intracellular lipid transport2019

    • Author(s)
      Yasunori Saheki
    • Organizer
      Organelle zones: opening a new era of Cell Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Understanding dynamic membrane contact sites in health and disease2019

    • Author(s)
      Yasunori Saheki
    • Organizer
      EMBO Young Investigator Meeting 2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Functional dissection of membrane contact sites in intracellular lipid transport2019

    • Author(s)
      Yasunori Saheki
    • Organizer
      New Frontiers in Synapse Biology and Brain Disorders
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Cross-talk between the endoplasmic reticulum and the plasma membrane mediated by the extended synaptotagmins2018

    • Author(s)
      Yasunori Saheki
    • Organizer
      15th Meeting of the Asian-Pacific Society for Neurochemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Functional dissection of intracellular lipid transport via mammalian cell biology and C. elegens genetics2018

    • Author(s)
      Yasunori Saheki
    • Organizer
      The 6th National Conference on Laboratory Animal Science (NCLAS) [organized by Laboratory Animal Science Association of Malaysia (LASAM)]
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Cross-talk between the endoplasmic reticulum and the plasma membrane mediated by the extended synaptotagmins2018

    • Author(s)
      Saheki Yasunori
    • Organizer
      The 6th International and the 15th National Symposium on Membrane Biology (ISMB2018)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cross-talk between the endoplasmic reticulum and the plasma membrane mediated by the extended synaptotagmins2018

    • Author(s)
      Saheki Yasunori
    • Organizer
      ISLS7: 7th International Singapore Lipid Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The regulation of intracellular lipid transport at membrane contact sites2018

    • Author(s)
      Saheki Yasunori
    • Organizer
      第15回生命資源研究・支援センター シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cross-talk between the endoplasmic reticulum and the plasma membrane mediated by the extended synaptotagmins2017

    • Author(s)
      Saheki Yasunori
    • Organizer
      Korean Society for Brain and Neural Science (KSBNS) Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 佐伯研究室ウェブサイト

    • URL

      https://www.thesahekilab.com

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report
  • [Remarks] 南洋理工大学医学部ウェブサイト

    • URL

      http://www.lkcmedicine.ntu.edu.sg/aboutus/Faculty-and-Staff/Pages/Yasunori-Saheki.aspx

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-23  

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