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Physiological aspects of HAF-4 and HAF-9, C.elegansABC transporters, which cause abnormal formation of lysosome-related organelle.

Research Project

Project/Area Number 19590066
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OHASHI Ayako  Iwate Medical University, 薬学部, 教授 (90272484)

Co-Investigator(Renkei-kenkyūsha) SHIRAISHI Hirohisa  岩手医科大学, 薬学部, 講師 (80393156)
TANJI Takahiro  岩手医科大学, 薬学部, 助教 (60453320)
NISHIKORI Kenji  岩手医科大学, 薬学部, 助手 (20563844)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsトランスポーター / オルガネラ / 生理機能 / 線虫 / グノム / 薬学 / バイオテクノロジー / 遺伝学
Research Abstract

TAP-like (TAPL ; ABCB9) is a half-type ATP-binding cassette (ABC) transporter that localizes in lysosome and putatively conveys peptides from cytosol to lysosome. However, the physiological role of this transporter remains to be elucidated. Comparison of genome databases reveals that TAPL is conserved in various species from a simple model organism, Caenorhabditis elegans, to mammals. C.elegans possesses homologous TAPL genes : haf-4 and haf-9. In this study, we examined the tissue-specific expression of these two genes and analyzed the phenotypes of the loss-of-function mutants for haf-4 and haf-9 to elucidate the in vivo function of these genes. Both HAF-4 and HAF-9 tagged with green fluorescent protein (GFP) were mainly localized on the membrane of nonacidic but lysosome-associated membrane protein homologue (LMP-1)-positive intestinal granules from larval to adult stage. The mutants for haf-4 and haf-9 exhibited granular defects in late larval and young adult intestinal cells, associated with decreased brood size, prolonged defecation cycle, and slow growth. The intestinal granular phenotype was rescued by the overexpression of the GFP-tagged wild-type protein, but not by the ATP-unbound form of HAF-4. These results demonstrate that two ABC transporters, HAF-4 and HAF-9, are related to intestinal granular formation and some other physiological aspects.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (28 results)

All 2010 2009 2008 2007 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (15 results) Remarks (2 results)

  • [Journal Article] Normal formation of a subset of intestinal granules in Caenorhabditis elegans requires ATP-binding cassette transporters HAF-4 and HAF-9, which are highly homologous to human lysosomal peptide transporter TAP-like2009

    • Author(s)
      Kawai H., Tanji T., Shiraishi H., Yamada M., Iijima R., Inoue T., Kezuka Y., Ohashi K., Yoshida Y., Tohyama K., Gengyo-Ando K., Mitani S., Arai H., Ohashi-Kobayashi A., Maeda M.
    • Journal Title

      Mol. Biol. Cell 20

      Pages: 2979-2990

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Normal formation of a subset of intestinal granules in Caenorhabditis elegans requires ATP-binding cassette transporters HAF-4 and HAF-9, which are highly homologous to human lysosomal peptide transporter TAP-like.2009

    • Author(s)
      Kawai H, et al.
    • Journal Title

      Mol Biol Cell. 20

      Pages: 2979-2990

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical characterization of transporter associated with antigen processing (TAP)-like (ABCB9) expressed in insect cells2008

    • Author(s)
      Ohara T., Ohashi-Kobayashi A., Maeda M.
    • Journal Title

      Biol. Pharm. Bull. 31

      Pages: 1-5

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic AMP-dependent proteolysis of GATA-6 expressed on the intracellular membrane2008

    • Author(s)
      Tsuge T., Uetani K., Sato R., Ohashi-Kobayashi A., Maeda M.
    • Journal Title

      Cell Biol. Int. 32

      Pages: 298-303

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional dissection of transmembrane domains of human TAP-like (ABCB9). Biochem.2008

    • Author(s)
      Kamakura A., Fujimoto Y., Motohashi Y., Ohashi K., Ohashi-Kobayashi A., Maeda M.
    • Journal Title

      Biophys. Res. Commun. 377

      Pages: 847-851

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential activation of the lectin and antimicrobial peptide genes in Sarcophaga peregrina (the flesh fly)2008

    • Author(s)
      Tanji T., Shiraishi H., Natori S., Ohashi-Kobayashi A.
    • Journal Title

      Arch. Insect Biochem. Physiol. 69

      Pages: 189-198

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional dissection of transmembrane domains of human TAP-like (ABCB9).2008

    • Author(s)
      Kamakura A, et al.
    • Journal Title

      Biochem Biophys Res Commun. 377

      Pages: 847-851

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical characterization of transporter associated with antigen processing(TAP)-like(ABCB9)expressed in insect cells.2008

    • Author(s)
      Ohara T, et. al.
    • Journal Title

      Biol.Pharm.Bull. 31

      Pages: 1-5

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic AMP-dependent proteolysis of GATA-6 expressed on the intracellular membrane.2008

    • Author(s)
      Tsuge T, et. al.
    • Journal Title

      Cell Biol.Int. 32

      Pages: 298-303

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ABC transporter TAP-like and TAP family2007

    • Author(s)
      Maeda M., Ohashi-Kobayashi A.
    • Journal Title

      Seikagaku 79

      Pages: 588-596

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] ABC transporter TAP-like and TAP family.2007

    • Author(s)
      Maeda M & Ohashi-Kobayashi A
    • Journal Title

      Seikagaku 79

      Pages: 588-596

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Functional analysis of lysosomal peptide transporters in C.elegans.(招待講演)2010

    • Author(s)
      Tanji T, et al
    • Organizer
      BIT Life Sciences' 3rd Annual Protein and Peptide Conference (PepCon-2010)
    • Place of Presentation
      北京(中国)
    • Year and Date
      2010-03-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] Functional analysis of lysosomal peptide transporters in C. elegans2010

    • Author(s)
      Takahiro Tanji, Hirohisa Shiraishi, Kenji Nishikori, Ayako Ohashi-Kobayashi
    • Organizer
      BIT Life Sciences' 3rd Annual Protein and Peptide Conference (PepCon-2010
    • Place of Presentation
      北京
    • Related Report
      2009 Final Research Report
  • [Presentation] Functional profile of a lysosomal ABC transporter HAF-2 in Caenorhabditis elegans.2009

    • Author(s)
      白石博久, 他
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Physiological roles of putative intracellular peptide ABC transporters in C.elegans intestine.2009

    • Author(s)
      Shiraishi H, et al
    • Organizer
      3rd Asia-Pacific International Peptide Symposium
    • Place of Presentation
      済州島(韓国)
    • Year and Date
      2009-11-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] Comparisons of the subcellular localization and mutant phenotypes of intracellular ABC transporters HAF-4 and HAF-9 with LMP-1 in C.elegans intestinal cells.2009

    • Author(s)
      Tanji T, et al
    • Organizer
      17th International C.elegans Meeting
    • Place of Presentation
      Los Angels(アメリカ)
    • Year and Date
      2009-06-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] Comparisons of the subcellular localization and mutant phenotypes of intracellular ABC transporters HAF-4 and HAF-9 with LMP-1 in C. elegans intestinal cells2009

    • Author(s)
      Takahiro Tanji, Hirohisa Shiraishi, Yasuo Yoshida, Koujiro Tohyama, Keiko Gengyo-Ando, Shohei Mitani, Masatomo Maeda, Ayako Ohashi-Kobayashi
    • Organizer
      17th International C. elegans meeting
    • Place of Presentation
      ロサンゼルス
    • Related Report
      2009 Final Research Report
  • [Presentation] Physiological roles of putative intracellular peptide ABC transporters in C. elegans intestine2009

    • Author(s)
      Hirohisa Shiraishi, Takahiro Tanji, Kenji Nishikori, Ayako Ohashi-Kobayashi
    • Organizer
      3rd Asia-Pacific International Peptide Symposium
    • Place of Presentation
      西帰浦
    • Related Report
      2009 Final Research Report
  • [Presentation] Functional profile of a lysosomal ABC transporter HAF-2 in Caenorhabditis elegans2009

    • Author(s)
      白石博久、丹治貴博、脇本菜有、安藤恵子、三谷昌平、前田正知、大橋綾子
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] 線虫腸細胞のリソソーム関連オルガネラ形成におけるABC輸送体HAF-4、HAF-9の役割(BMB20082008

    • Author(s)
      白石博久、丹治貴博、吉田康夫、遠山稿二郎、前田正知、大橋綾子
    • Organizer
      第31回日本分子生物学会・第81回日本生化学会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2009 Final Research Report
  • [Presentation] 線虫の補体系因子C3様蛋白thioester- containing protein (TEP)の発現解析(BMB20082008

    • Author(s)
      丹治貴博、白石博久、大橋綾子
    • Organizer
      第31回日本分子生物学会・第81回日本生化学会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2009 Final Research Report
  • [Presentation] 線虫リソソーム関連輸送体の変異体に見られる腸内オルガネラ異常の解析~透過型電子顕微鏡を用いた超微細構造の観察~2008

    • Author(s)
      白石博久、吉田康夫、丹治貴博、遠山稿二郎、大橋綾子
    • Organizer
      第47回日本薬学会東北支部大会
    • Place of Presentation
      矢巾
    • Year and Date
      2008-10-26
    • Related Report
      2009 Final Research Report
  • [Presentation] Role of the Caenorhabditis elegans ABC transporter genes in the biogenesis of intestinal lysosome-related organelle2008

    • Author(s)
      Takahiro Tanji, Hirohisa Shiraishi, Yasuo Yoshida, Koujiro Tohyama, Mitsuo Yamada, Masatomo Maeda, Ayako Ohashi-Kobayashi
    • Organizer
      2008 East Asia C. elegans Meeting
    • Place of Presentation
      上海
    • Related Report
      2009 Final Research Report
  • [Presentation] 線虫におけるリソソーム関連ABCトランスポーターの役割2007

    • Author(s)
      白石博久、丹治貴博、吉田康夫、遠山稿二郎、山田光男、前田正知、大橋綾子
    • Organizer
      トランスポーター研究会第1回東北部会
    • Place of Presentation
      仙台
    • Year and Date
      2007-11-25
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] 線虫C. elegansのABC輸送体haf-2の発現解析2007

    • Author(s)
      脇本菜有、大橋-小林綾子、安藤恵子、三谷昌平、前田正知
    • Organizer
      BMB2007第30回日本分子生物学会年会、第80回日本生化学会大会合同年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] 線虫C.elegansのABC輸送体haf-2の発現解析2007

    • Author(s)
      脇本 菜有, 他
    • Organizer
      BMB2007第30回日本分子生物学会年会、第80回日本生化学会大会合同年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Remarks] 線虫データベースWormBaseに文献登録

    • URL

      http://www.wormbase.org/db/misc/biblio?name=WBGene00001814;class=Gene

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.wormbase.org/db/misc/biblio?name=WBGene00001819;class=Gene

    • Related Report
      2009 Final Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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