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Functions and modes of action of small G proteins in cell adhesion and migration

Research Project

Project/Area Number 11680632
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokushima School of Medicine (2000)
Osaka University (1999)

Principal Investigator

SASAKI Takuya  The University of Tokushima School of Medicine Department of Biochemistry Professor, 医学部, 教授 (40241278)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordscell migration / vesicle transport / Rab family / Rab11 / Rabphilin-11 / microtubule / mSec13 / recycling / 細胞骨格 / Rhoファミリー低分子量G蛋白質
Research Abstract

When epithelial cells start to migrate, cell-cell junctions are first disrupted. During migration, membrane protrusions, such as lamellipodia and filopodia, at the cell front, and retraction at the cell rear are externally observed, and dynamic reorganization of the actin cytoskeleton is internally observed. We have recently clarified that the Rho and Rab family small G proteins coordinately regulate cell adhesion and migration of cultured MDCK cells. The Rab family consists of over thirty members. We have found that some Rab family members are involved in HGF- or phorbol esterinduced endocytosis and recycling of cadherin and integrin. Rab11, a member of Rab family, has been implicated in vesicle recycling. During this support from 1999 to 2000, we have focused on studying the function and mode of action of Rab11 in cell migration. The results obtained are as follows :
(1) We have isolated a downstream target of Rab11, named Rabphilin-11, from bovine brain. We have found that rabphilin-11 is localized at perinuclear regions, presumably the Golgi complex and recycling endosomes in MDCK cells.
(2) We have found that Rabphilin-11 is localized not only at perinuclear regions but also along microtubules, which are oriented toward membrane lammelipodia in HeLa cells cultured on fibronectin. Overexpression of rabphilin-11 mutant reduces accumulation of transferrin at perinuclear regoins and cell migratoin.
(3) We have found that rabphilin-11 directly binds the mammalian counterpart of yeast Sec13 proteins (mSec13) in cell-free and intact cell systems. Disruption of the rabphilin-11-mSec13 interaction by overexpression of the mSec13-binding region of rabphilin-11 impairs vesicle trafficking.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Tanaka,M.: "Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction."Mol.Biol.Cell. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagano,F.: "Purification and properties of Rab3 GTPase activating protein."Methods Enzymol.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shirataki,H.: "Rabphilin-3 : a target molecule for Rab3 small G proteins."Methods Enzymol.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Orita,S.: "Doc2α as a modulator of Ca^<2+>-dependent exocytosis."Methods Enzymol.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takai,Y.: "Small GTP-binding proteins."Physiol.Rev.. 81. 153-208 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mammoto,A.: "Physical and functional interaction of Rabphilin-11 with mammalian Sec13-Implication in vesicle trafficking."J.Biol.Chem.. 275. 13167-13170 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaki,H.: "Role of Rab GDP dissociation inhibitor α in regulating plasticity of hippocampal neurotransmission."Proc.Natl.Acad.Sci.USA. 97. 11587-11592 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki,T.: "Rho family GTPase Cdc42 is essential for the acint-based motility of Shigella in mammalian cells."J.Exp.Med.. 191. 1905-1920 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mammoto,A.: "Stimulation of Rho GDI release by ERM proteins."Methods Enzymol.. 325. 91-101 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mammoto,A.: "RabllBP/Rabphilin-11-A downstream target of rab11 small G protein implicated in vesicle recycling."J.Biol.Chem.. 274. 25517-25524 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakaguchi,G.: "Doc2α is an activity-dependent presynaptic modulator of neurotransmitter release."Eur.J.Neurosci.. 11. 4262-4268 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Asakura,T.: "Similar and differential behavior between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells."Genes Cells. 4. 573-581 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi,H.: "Isolation of regulatory proteins for the Rab3 subfamily GTPases."Methods Mol.Biol.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka, M., et al.: "Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction."Mol.Biol.Cell. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nagano, F., et al.: "Purification and properties of Rab3 GTPase activating protein."Methods Enzymol.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shirataki, H., et al.: "Rabphilin-3 : a target molecule for Rab3 small G proteins."Methods Enzymol.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Orita, S., et al.: "Doc2α as a modulator of Ca^<2+>-dependent exocytosis."Methods Enzymol.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takai, Y., et al.: "Small GTP-binding proteins."Physiol.Rev.. 81. 153-208 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mammoto, A., et al.: "Physical and functional interaction of Rabphilin-11 with mammalian Sec13-Implication in vesicle trafficking."J.Biol.Chem.. 275. 13167-13170 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaki, H., et al.: "Role of Rab GDP dissociation inhibitor α in regulating plasticity of hippocampal neurotransmission."Proc.Natl.Acad.Sci.USA. 97. 11587-11592 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki, T., et al.: "Rho family GTPase Cdc42 is essential for the actin-based motility of Shigella in mammalian cells."J.Exp.Med.. 191. 1905-1920 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mammoto, A., et al.: "Stimulation of Rho GDI release by ERM proteins."Methods Enzymol.. 325. 91-101 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mammoto, A., et al.: "RabllBP/Rabphilin-11-A downstream target of rab11 small G protein implicated in vesicle recycling."J.Biol.Chem.. 274. 25517-25524 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakaguchi, G., et al.: "Doc2α is an activity-dependent presynaptic modulator of neurotransmitter release."Eur.J.Neurosci.. 11. 4262-4268 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Asakura, T., et al.: "Similar and differential behavior between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells."Genes Cells. 4. 573-581 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi, H., et al.: "Isolation of regulator proteins for the Rab3 subfamily GTPases."Methods Mol.Biol.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,M.: "Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction."Mol.Biol.Cell. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagano,F.: "Purification and properties of Rab3 GTPase activating protein."Methods Enzymol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shirataki,H.: "Rabphilin-3 : a target molecule for Rab3 small G proteins."Methods Enzymol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Orita,S.: "Doc2α as a modulator of Ca^<2+>-dependent exocytosis."Methods Enzymol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takai,Y.: "Small GTP-binding proteins."Physiol.Rev.. 81. 153-208 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mammoto,A.: "Physical and functional interaction of Rabphilin-11 with mammalian Sec13-Implication in vesicle trafficking."J.Biol.Chem.. 275. 13167-13170 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishizaki,H.: "Role of Rab GDP dissociation inhibitor αin regulating plasticity of hippocampal neurotransmission."Proc.Natl.Acad.Sci.USA. 97. 11587-11592 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzuki,T.: "Rho family GTPase Cdc42 is essential for the actin-based motility of Shigella in mammalian cells."J.Exp.Med.. 191. 1905-1920 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mammoto,A.: "Stimulation of Rho GDI release by ERM proteins."Methods Enzymol.. 325. 91-101 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi,H.: "Methods Mol.Biol."Isolation at regulatory proteins for the Rab3 subfamily GTPases.(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mammoto A.: "Ra11BP/Rabphilin-11 - A downstream target of rab11 small G protein implicated in vesicle recycling"J. Biol. Chem.. 274・36. 25517-25524 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakaguchi G.: "Doc2α is an activity-dependent modulator of excitatory synaptic transmission"Eur. J. Neurosci.. 11・12. 4262-4268 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Asakura T.: "Similar and differential behavior between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells"Genes Cells. 4・10. 573-581 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mammoto A.: "Physical and functional interaction of rabphilin-11 with mammalian sec13 protein. Implication in vesicle trafficking"J. Biol. Chem. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Orita S.: "Doc2α as a modulator of Ca^<2+> -dependent exocytosis"Methods Enzymol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mammoto A.: "Stimulation of Rho GDI release by ERM proteins"Methods Enzymol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Orita S.: "Frontiers of Neural Development"Springer-Verlag Tokyo Inc.,Tokyo. 444-449 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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