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Cell motility and the backward bulk flow of the plasma membrane components

Research Project

Project/Area Number 14380340
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOSAKA BIOSCIENCE INSTITUTE

Principal Investigator

SABE Hisataka  Osaka Bioscience Institute, Dept.of Molecuar Biology, Head, 分子生物学部門, 研究部長 (40187282)

Co-Investigator(Kenkyū-buntansha) YAGI Ryohei  Osaka Bioscience Institute, Dept.of Molecuar Biology, Research Fellow, 分子生物学部門, 日本学術振興会特別研究員
YANO Hajime  Osaka Bioscience Institute, Dept.of Molecuar Biology, Research Associate, 分子生物学部門, 研究員 (00284414)
HASHIMOTO Shigeru  Osaka Bioscience Institute, Dept.of Molecuar Biology, Research Associate, 分子生物学部門, 研究員 (50311303)
HASHIMOTO Ari  Osaka Bioscience Institute, Dept.of Molecuar Biology, Research Fellow, 分子生物学部門, 日本学術振興会特別研究員
近藤 明子  (財)大阪バイオサイエンス研究所, 分子生物学部門, 日本学術振興会特別研究員
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 2003: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2002: ¥10,900,000 (Direct Cost: ¥10,900,000)
Keywordscell motility / Art6 / ArtGAP / AMAP2 / PAG3 / endocytosis / endosomal recycling / amphiphysin / cancer cell invasion / endosomal recycling
Research Abstract

Previously we reported that AMAP2/PAG3/Papα/KIAAO400, a GTPase-activating protein (GAP), acts to antagonize Arf6 function when overexpressed, while it was shown to exhibit efficient GAPing activities for other Arf isoforms in vitro. During this period of the two fiscal years we first found that AMAP2, through its ArfGAP domain, binds to GTP-Arf6, but not to GDP-Arf6 nor other Arfs irrespective of nucleotide status. The majority of AMAP2 was localized to intracellular tubulovesicular structures, and redistributed to Arf6-enriched membrane areas upon Arf6 activation. In HeLa cells, Arf6 has been shown to be involved in the clathrin-independent endocytosis of Tac, but not the clathrin-dependent endocytosis of transferrin. We found that Arf6 silencing inhibited the internalization of Tac, but not transferrin, in HeLa cells. Internalization of Tac, but not transferrin, was also significantly inhibited by AMAP2 silencing and overexpression. AMAP2 was moreover found to bind to amphiphysin-IIm, a component of the endocytic machinery, via its proline-rich domain. We propose that AMAP2 has dual mechanisms for its function ; it exhibits efficient catalytic GAP activity for the class I and III Arfs, and yet is involved in the cellular function of the class III Arf without immediate GAPing activity. These dual mechanisms of AMAP2 may be important for the cellular function of GTP-Arf6.
During analyzing physiological roles of AMAP1, another paxillin-binding ArfGAP we have previously isolated, we found that this protein is localized to invadopodia of breast cancer cells and plays an essential role for the invasion. Since AMAP1 acts to antagonize Arf6, we also analyzed possible role of Arf6 in cancer invasion, and found that Arf6 is also essential for breast cancer invasion. We have proposed that Arf6, and the intracellular machinery regulating Arf6 during invasion, should be considered as therapeutic targets for the prevention of breast cancer invasion.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] H.Yano, Y.Mazaki, K.Kurokawa, K.Steven, Hanks, M.Matsuda, H.Sabe: "Roles played by a subset of integrin-signaling molecules in cadherin-based cell-cell adhesion."J.Cell Biol.. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Watanabe, T.Shimizu, J.Nishihira, R.Abe, T.Nakayama, M.Taniguchi, H.Sabe, T.Ishibashi, H.Shimizu: "Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor(MIF) in human dermal fibroblasts."J.Biol.Chem.. 279・3. 1676-1683 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Hashimoto, Y.Onodera, A.Hashimoto, M.Tanaka, M.Hamaguchi, A.Yamada, H.Sabe: "Requirement for Arf6 in breast cancer invasive activities."Proc.Natl.Acad.Sci.USA. 101・17. 6647-6652 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Sabe: "A requirement for Arf6 in cell adhesion and migration, and cancer cell invasion."J.Biochem.. 134・4. 485-489 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] C.Didier, L.Broday, A.Bhoumik, S.Israeli, S.Takahashi, K.Nakayama, S.M.Thomas, C.E.Turner, S.Henderson, H.Sabe, Z.Ronai: "RNF5 - a RING finger protein that regulates cell motility by targeting paxillin ubiquitination and altered localization."Mol.Cell Biol.. 23・15. 5331-5345 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Tsubouchi, J.Sakakura, R.Yagi, Y.Mazaki, E.Schaefer, H.Yano, H.Sabe: "Tyrosine phosphorylation of paxillin is important for microtubule organizing center positioning and directional persistency in motile epithelial cells."J.Cell Biol.. 159・4. 673-683 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yamamoto, T.Maruyama, N.Sakai, R.Sakurai, A.Shimizu, T.Hamatani, H.Masuda, H.Uchida, H.Sabe, Y.Yoshimura: "Expression and subcellular distribution of the active form of c-Srctyrosine kinase in differentiating human endometrial stromal cells."Mol.Hum.Reprod.. 8・12. 1117-1124 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Oshiro, S.Koyama, S.Sugiyama, A.Kondo, Y.Onodera, T.Asahara, H.Sabe, A.Kikuchi: "Interaction of POBI, a downstream molecule of small G protein Ral, with PAG2, a paxillin binding protein, is involved in cell migration."J.Biol.Chem.. 277・41. 38618-38626 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.J.Woods, M.S.Roberts, J.Choudhary, S.T.Barry, Y.Mazaki, H.Sabe, S.J.Morley, D.R.Critchley, J.C.Norman: "Paxillin associates with poly(A)-binding protein lat the dense ER and the leading edge of migrating cells."J.Biol.Chem.. 277・8. 6428-6437 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Iwasaki, A.Nakata, M.Mukai, K.Shinkai, H.Yano, H.Sabe, E.Schaefer, M.Tatsuta, T.Tsujimura, N.Terada, E.Kakishita, H.Akedo: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration."Int.J.Cancer. 97・3. 330-335 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Sabe: "Protein and Cell Regulation Vol.1(Ed.R.Kahn)"Kluwer Academic Publishers. 23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Yano, Y.Mazaki, K.Kurokawa, K.Steven, Hanks, M.Matsuda, H.Sabe: "Roles played by a subset of integrin-signaling molecules in cadherin-based cell-cell adhesion."J.Cell Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Watanabe, T.Shimizu, J.Nishihira, R.Abe, T.Nakayama, M.Taniguchi, H.Sabe, T.Ishibashi, H.Shimizu: "Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fibroblasts."J.Biol.Chem.. 279(3). 1676-1683 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Hshimoto, Y.Onodera, A.Hashimoto, M.Tanaka, M.Hamaguchi, A.Yamada, H.Sabe.: "Requirement for Arf6 in breast cancel-invasive activities."Proc.Natl.Acad.Sci.USA.. 101(17). 6647-6652 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Sabe: "PASILLIN-ASSOSJATED ARF GAPS : their Isoform Specificities and Roles in Coordination."Protein and cell regulation(Ed.R.Kahn)(Kluwer Academic Publishers). vol.1. 185-207 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Sabe: "Requirement for Arf6 in cell adhesion and migration, and cancer cell invasion."J.Biochem.Minireview. 134(4). 485-489 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] C.Didier, L.Broday, A.Bhoumik, S.Israeli, S.Takahashi, K.Nakayama, S.M.Thomas, C.B.Turner, S.Henderson, H.Sabe, Z.Ronai.: "RNF5-a RHNG finger protein that regulates cell motility by targeting paxillin ubiquitination and alteredlocalization."Mol.Cell Biol. 23(15). 5331-5345 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Tsubouchi, J.Sakakura, R.Yagi, Y.Mazaki, E.Schaefer, H.Yano, H.Sabe: "Tyrosine phosphorylation of paxillin is important for microtubule organizing center positioning and directional persistency in motile epithelial cells"J.Cell Biol.. 159(4). 673-683 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yamamoto, T.Maruyama, N.Sakai, R.Sakurai, A.Shimizu, T.Hamatani, H.Masuda, H.Uchida, H.Sabe, Y.Yoshimura.: "Expression and subcellular distribution of the active form of c-Src tyrosine kinase in differentiatinghuman endometrial stromal cells."Mol.Hum.Reprod. 8(12). 1117-1124 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Oshiro, S.Koyama, S.Sugiyama, A.Kondo, Y.Onodera, T.Asahara, H.Sabe, A.Kikuchi.: "Interaction of POB 1, a downstream molecule of small G protein Ra1, with PAG2, a paxillin binding protein, is involved in cell migration."J.Biol.Chem.. 277(41). 38618-38626 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.J.Woods, M.S.Roberts, J.Choudhary, S.T.Barry, Y.Mazaki, H.Sabe, S.J.Morley, D.R.Critchley, J.C.Norman.: "Paxillin associates with poly(A)-binding protein lat the dense ER and the leading edge of migrating cells"J.Biol.Chem. 288(8). 6428-6437 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Iwasaki, A.Nakata, M.Mukai, K.Shinkai, H.Yano, E.Schaefer, M.Tatsuta, T.Tsujimura, N.Terada, B.Kakishita, H.Akedo.: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration.cells."Int.J.Cancer. 97(3). 330-335 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Watanabe, T.Shimizu, J.Nishihira, R.Abe, T.Nakayama, M.Taniguchi, H.Sabe, T.Ishibashi, H.Shimizu.: "Ultravialet A-induced production of matrix metalloproteinase-1 is mediated by macrophagemigration inhibitory factor in human dermal Ifibroblasts."J Biol.Chem.. 279・3. 1676-1683 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Sabe.: "A requirement for Arf6 in cell adhesion and migration, and cancer cell invasion."J.Biochem.Minireview. 134・4. 485-489 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] C.Didier, L.Broday, A.Bhoumik, S.Israeli, S.Takahashi, K.Nakayama, S.M.Thomas, C.E.Turner, S.Henderson, H.Sabe, Z.Ronai.: "RNF5 - a RING finger protein that regulates cell motility by targeting paxillin ubiquitination and altered localization."Mol.Cell Biol.. 23・15. 5331-5345 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Sabe.: "The ARF book(Ed.R.Kahn)"Kiuwer Academic Publishers.(in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Tsubouchi, J.Sakakura, R.Yagi, Y.Mazaki, E.Schaefer, H.Yano, H.Sabe: "Tyrosine phosphorylation of paxillin is important for microtubule organizing center positioning and directional persistency in motile epithelial cells"J. Cell Biol.. 159・4. 673-683 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Yamamoto, Y.Maruyama, N.Sakai, R.Sakurai, A.Shimitu, T.Hamatani, H.Masuda, H.Uchida, H.Sabe, Y.Yoshimura: "Expression and subcellular distribution of the active form of c-Src tyrosine kinase in differentiating human endometrial stromal cells"Mol. Hum. Reprod.. 8・12. 1117-1124 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Oshiro, S.Koyama, S.Sugiyama, A.Kondo, Y.Onodera, T.Asahara, H.Sabe, A.Kikuchi: "Interaction of POB1, a downstream molecule of small G protein Ra1, with PAG2, a paxillin binding protein, is involved in cell migration"J. Biol. Chem.. 277・41. 38618-38626 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.J.Woods, M.S.Roberts, J.Choudhary, S.T.Barry, Y.Mazaki, H.Sabe, S.J.Morley, D.R.Critchley, J.C.Norman: "Paxillin associates with poly(A)-binding protein 1 at the dense ER and the leading edge of migrating cells"J. Biol. Chem.. 277・8. 6428-6437 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwasaki, T., Nakata, A., Mukai, M., Shinkai, K., Yano, H., Sabe, H., Schaefer, E., Tatsuta, M., Tsujimura, T., Terada, N., Kakishita, E., Akedo, H.: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration"Int. J. Cancer. 97・3. 330-335 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Sabe: "In 'The ARF book'"Kluwer Academic Publishers. (Ed. R.Kahn)(in press). 18

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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