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Traffic and expression of membrane proteins regulated by an ubiquitin-lysosome system

Research Project

Project/Area Number 18590059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyushu University

Principal Investigator

FUJITA Hideaki  Kyushu University, Graduate School of Pharmaceutical Sciences, Assistant Professor (80291524)

Co-Investigator(Kenkyū-buntansha) 田中 嘉孝  九州大学, 薬学研究院, 教授 (20217095)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsubiquitin / lvsosome / proteolvsis / endosome / 鉄イオン代謝 / エンドサイトーシス
Research Abstract

Although the significance of ubiquitin-signals for both endocytosis from the plasma membrane (PM) and sorting at trans-Golgi network (TGN) and endosomes/multivesicular body has been postulated, the proteins whose trafficking is regulated by ubiquitylation are poorly understood. SKD1 (E235Q), an ATPase-deficient form of SKD1/Vps4B, abrogates the recycling of ubiquitin from the ubiquitylated proteins accumulated in aberrant endosomes(EQ compartment; mammalian class E vps compartment). We have taken advantage of this to identify substrates for ubiquitylation using a combination of affinity purification and LC-MS/MS. A variety of receptors, transporters, cell adhesion and signaling molecules localized to the PM are identified, and most of them are accumulated in EQ compartment in an ubiquitylation-dependent manner. Moreover, integral membrane protein 2B and Nedd4-interacting protein 2 are the first examples in mammalian cells, of proteins whose trafficking between the Golgi/TGN and endosomes is regulated by ubiquitylation. Intriguingly trafficking of transferrin receptor (TfR) is highly correlated with its ubiquitylation state, since free ubiquitin depletion inhibits ubiquitylation of TfR and resumes its accumulation in EQ compartments. Taken together, the identified proteins are the best candidates for the membrane-associated proteins whose trafficking is regulated by ubiquitylation. These data provide us forward steps to identify the mechanistic basis for ubiquitin-dependent protein sorting.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (6 results)

All 2007

All Journal Article (3 results) (of which Peer Reviewed: 2 results) Presentation (3 results)

  • [Journal Article] "A role for Rab5 avtivity in the biogenesis of endosomal and lysosomal compartment"2007

    • Author(s)
      Y.Hirota, T.Kuronita, H.Fujita and Y.Tanaka
    • Journal Title

      Biochem.Biophy.Res.Commun 364(1)

      Pages: 40-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A role for Rab5 activity in the biogenesis of endosomal and lysosomal compartment2007

    • Author(s)
      Y., Hirota, T., Kuronita, H., Fuiita , Y., Tanaka
    • Journal Title

      Biochem. Biophy. Res. Commun 364(1)

      Pages: 40-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Arole for RabS activity in the biogenesis of endosomal and lysosomal compartment2007

    • Author(s)
      Y. Hirota, T. Kuronita, H. Fujita, Y. Tanaka
    • Journal Title

      Biochem.Biophy.res.Commun 364(1)

      Pages: 40-47

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] "A Proteomics Analysis of Membrane-associated Proteins. Those Trafficking to Lysosomes Is Regulated by An Ubiquitylation"2007

    • Author(s)
      H.Fujita, M.Matsumoto, K.Yamanaka and Y.Tanaka
    • Organizer
      日本プロテオーム機構第五回大会(シンポジウム)
    • Place of Presentation
      東京
    • Year and Date
      2007-07-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A Proteomics Analysis of Membrane-associated Proteins Those Trafficking toLysosomes Is Regulated by An Ubiquitylation2007

    • Author(s)
      H. Fujita, M. Matsumoto, K.Yamanaka and Y.Tanaka
    • Organizer
      日本プロテオーム機構第五回大会(シンポジウム)
    • Place of Presentation
      東京
    • Year and Date
      2007-07-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] A Proteomics Analysis of Membrane-associated Proteins Those Trafficking to Lysosomes Is Regulated by An Ubiquitylation2007

    • Author(s)
      H., Fujita, M., Matsumoto, KI., Yamanaka, Y., Tanaka
    • Organizer
      5th Japan Human Proteome
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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