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Regulation of amyloid-beta clearance by the small GTPase Arf6 and the phospholipid kinase PIP5K

Research Project

Project/Area Number 24770116
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

FUNAKOSHI Yuji  筑波大学, 医学医療系, 助教 (30415286)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsArf6 / PIP5K / βアミロイド / 細胞内輸送 / Megalin / LRP1 / アミロイドβ / 膜輸送 / 低分子量G蛋白質Arf6 / リン脂質キナーゼPIP5K
Research Abstract

The plasma membrane receptors Megalin and LRP1, play a pivotal role in elimination of the Amyloid-beta peptide (Abeta), which is crucially involved in Alzheimer's disease, from the brain. In brain microvascular endothelial cells and choroid plexus epithelial cells, both receptors uptake Abeta from the brain fluid and transport them to the blood. In this research we find that the small GTPase Arf6 and the phospholipid kinase PIP5K bind to the cytoplasmic domains of Megalin and LRP1. We also demonstrate that knockdown of Arf6 causes accumulation of Megalin and LRP1 at intracellular endosomes and significant increase of the expression level of those proteins. These results indicate that Arf6 regulates transport of Megalin and LRP1 to lysosomes for degradation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (14 results)

All 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Anti prolifetative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB.2013

    • Author(s)
      Ogami, K., Hosoda, N., Funakoshi, N., Hoshino, S.
    • Journal Title

      Oncogene

      Volume: - Issue: 1 Pages: 55-64

    • DOI

      10.1038/onc.2012.548

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induce d superoxide generation and degranulation in mouse neutrophils : phospholipase D is dispensable2013

    • Author(s)
      Sato T., Hongu T., Sakamoto M., Funakoshi Y., Kanaho Y.
    • Journal Title

      Mol. Cell. Biol.

      Volume: 33 Issue: 1 Pages: 136-145

    • DOI

      10.1128/mcb.00869-12

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of fMLP-induced superoxide generation and degranulation in mouse neutrophils2013

    • Author(s)
      Kanaho Y., Sato T., Hongu T., Funakoshi Y.
    • Journal Title

      Adv. Biol. Reg.

      Volume: 63 Issue: 1 Pages: 128-134

    • DOI

      10.1016/j.jbior.2012.09.001

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antiproliferative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB.2013

    • Author(s)
      Ogami K, Hosoda N, Funakoshi Y, Hoshino S.
    • Journal Title

      Oncogene

      Volume: 未定

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation and degranulation in mouse neutrophils: phospholipase D is dispensable.2013

    • Author(s)
      Sato T, Hongu T, Sakamoto M, Funakoshi Y, Kanaho Y.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 33 Pages: 136-145

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of fMLP-induced superoxide generation and degranulation in mouse neutrophils.2013

    • Author(s)
      Kanaho Y, Sato T, Hongu T, Funakoshi Y.
    • Journal Title

      Advances in Biological Regulation

      Volume: 63 Pages: 128-134

    • Related Report
      2012 Research-status Report
  • [Journal Article] Phosphatidylinositol 4-phosphate 5-kinase is indispensable for mouse spermatogenesis2012

    • Author(s)
      Hasegawa, H., Noguchi, J., Yamashita, M., Okada, R., Sugimoto, R., Furuya, M., Unoki, T., Funakoshi, Y., Baba, T., and Kanaho, Y.
    • Journal Title

      Biol. Reprod

      Volume: 86 Issue: 5 Pages: 1-12

    • DOI

      10.1095/biolreprod.110.089896

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosphatidylinositol 4-phosphate 5-kinase is indispensable for mouse spermatogenesis.2012

    • Author(s)
      Hasegawa H, Noguchi J, Yamashita M, Okada R, Sugimoto R, Furuya M, Unoki T, Funakoshi Y, Baba T, Kanaho Y.
    • Journal Title

      Biology of Reproduction

      Volume: 86 Pages: 1-12

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Ubiquitin-specific prtotease TRE17/USP6 targets clathrin-independent cargo to recycling2013

    • Author(s)
      Yuji Funakoshi, Yasunori Kanaho, Julie G. Donaldson
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] リン脂質代謝酵素ホスホリパーゼD2は腫瘍形成を抑制する2013

    • Author(s)
      本宮綱記、船越祐司、金保安則
    • Organizer
      第55回日本脂質生化学会
    • Place of Presentation
      宮城県松島町
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Ubiquitin-specific protease TRE17/USP6 targets clathrin-independent cargo to recycling2013

    • Author(s)
      Yuji Funakoshi, Yasunori Kanaho, Julie G. Donaldson
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Ubiquitin-specific prtotease TRE17/USP6 targets clathrin-independent cargo to recycling2012

    • Author(s)
      Funakoshi Y, Kanaho Y, Donalson JD
    • Organizer
      2012 American Society for Cell Biology, Annual Meeting
    • Place of Presentation
      サンフランシスコ、アメリカ合衆国
    • Related Report
      2013 Final Research Report
  • [Presentation] Ubiquitin-specific protease TRE17/USP6 targets clathrin-independent cargo to recycling2012

    • Author(s)
      Funakoshi Y, Kanaho Y, Donaldson JG
    • Organizer
      2012 American Society for Cell Biology, Annual Meeting
    • Place of Presentation
      サンフランシスコ、アメリカ合衆国
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.md.tsukuba.ac.jp/basic-med/biochem/kanaholab/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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