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A novel role of CLPTM1 in the ER-associated degradation of membrane proteins

Research Project

Project/Area Number 24658262
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Clinical veterinary science
Research InstitutionHokkaido University

Principal Investigator

INABA MUTSUMI  北海道大学, (連合)獣医学研究科, 教授 (00183179)

Co-Investigator(Kenkyū-buntansha) SATO Kota  北海道大学, 大学院獣医学研究科, 准教授 (50283974)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords小胞体関連分解 / プロテアソーム系 / 膜蛋白質 / 小胞体品質管理 / シャペロン / ERシャペロン / 臨床病態 / 小胞体 / 品質管理 / 生体膜 / プロテアソーム
Research Abstract

The ER-associated degradation (ERAD) of various polytopic membrane proteins involves recognition of the polypeptide in the ER and its retrotranslocation into the cytosol, leading to its degradation by the proteasome system. The purpose of the present study was to unravel the role of CLPTM1 in the ERAD of an AE1 anion exchanger mutant, R664X AE1, with characteristic features of ubiquitin- and glycosylation-independence. In HEK293 cells expressing the AE1 mutant, CLPTM1 was localized in the ER and associated with several ER chaperone proteins including KIAA0090, p97/VCP, Derlins, and calnexin. However, overexpression or suppression of CLPTM1 had no apparent effect on proteasomal degradation of R664X AE1. In contrast, overexpression of KIAA0090 and/or p97/VCP accelerated the proteasomal degradation of the mutant.

Report

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

    (13 results)

All 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (6 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] A new class of endoplasmic reticulum transmembrane proteins and its selective interaction with Sec24C2013

    • Author(s)
      Otsu, W., Kurooka, T., Otsuka, Y., Sato, K. and Inaba, M
    • Journal Title

      J. Biol. Chem

      Volume: (in press) Issue: 25 Pages: 18521-18532

    • DOI

      10.1074/jbc.m112.443325

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulatory roles of NHERF1 and NHERF2 in cell surface expression of the glutamate transporter GLAST2013

    • Author(s)
      Sato, K., Otsu, W., Otsuka, Y., and Inaba. M.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 833 Pages: 839-845

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulatory roles of NHERF1 and NHERF2 in cell surface expression of the glutamate transporter GLAST.2013

    • Author(s)
      Sato, K., Otsu, W., Otsuka, Y., and Inaba, M.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 833 Pages: 839-845

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulatory roles of NHERF1 and NHERF2 in cell surface expression of the glutamate transporter GLAST2013

    • Author(s)
      Sato, K., Otsu, W., Otsuka, Y., Inaba, M.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 430(2) Issue: 2 Pages: 839-845

    • DOI

      10.1016/j.bbrc.2012.11.059

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clathrin-mediated endocytosis of mammalian erythroid AE1 anion exchanger facilitated by a YXXΦor a canonical YXXXΦmotif in the N-terminal stretch2012

    • Author(s)
      Wang, C.-C., Sato, K., Otsuka, Y., Otsu, W., and Inaba, M.
    • Journal Title

      J. Vet. Med. Sci

      Volume: 74 Pages: 17-25

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clathrin-mediated Endocytosis of Mammalian Erythroid AE1 Anion Exchanger Facilitated by a YXX.PHI. or a Noncanonical YXXX.PHI. Motif in the N-Terminal Stretch2012

    • Author(s)
      Wang CC., Sato K., Otsuka Y., Otsu W., Inaba M.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 74 Issue: 1 Pages: 17-25

    • DOI

      10.1292/jvms.11-0345

    • NAID

      130001032919

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Endoplasmic reticulum-associated degradation of a bovine AE1 mutant : Interaction of R664X AE1 with ER chaperones and dislocation channel proteins2013

    • Author(s)
      Otsu, W., Otsuka, Y., Miyazono, K., Sato, K., and Inaba, M
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2013-09-11
    • Related Report
      2013 Final Research Report
  • [Presentation] アニオン交換輸送体AE1の小胞体関連分解メカニズム : 小胞体関連蛋白質との相互作用2013

    • Author(s)
      大津航、宮園耕介、大塚弥生、佐藤耕太、稲葉睦
    • Organizer
      日本膜学会第35年会
    • Place of Presentation
      早稲田大学理工学部、東京
    • Year and Date
      2013-05-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Endoplasmic reticulum-associated degradation of a bovine AE1 mutsnt: Interaction of R664X AE1 with ER chaperones and dislocation channel proteins.2013

    • Author(s)
      Otsu, W., Otsuka, Y., Miyazono, K., Sato, K., and Inaba, M.
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] R664X変異Anion Exchanger 1 (AE1) の小胞体関連分解:AE1と小胞体蛋白質との相互作用2013

    • Author(s)
      大津 航、宮園 耕介、大塚 弥生、佐藤 耕太、稲葉 睦
    • Organizer
      日本膜学会第35年会
    • Place of Presentation
      早稲田大学理工学部(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] R664X変異Anion Exchanger 1 (AE1)の小胞体関連分解 : AE1と小胞体蛋白質との相互作用2012

    • Author(s)
      大津航、宮園耕介、大塚弥生、佐藤耕太、稲葉睦
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場、福岡
    • Year and Date
      2012-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] R664X変異Anion Exchanger 1 (AE1) の小胞体関連分解:AE1と小胞体蛋白質との相互作用2012

    • Author(s)
      大津 航、宮園 耕介、大塚 弥生、佐藤 耕太、稲葉 睦
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.vetmed.hokudai.ac.jp/organization/lmm/index.html

    • Related Report
      2013 Final Research Report

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

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