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2000 Fiscal Year Final Research Report Summary

ROLES OF GTP-BINDING PROTEINS IN THE FORMATION OF INTRACELLULAR TRANSPORT VESICLES

Research Project

Project/Area Number 09480148
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionUNIVERSITY OF TSUKUBA

Principal Investigator

NAKAYAMA Kazuhisa  INSTITUTION, UNIVERSITY OF TSUKUBA INSTITUTE OF BIOLOGICAL SCIENCES, ASSOCIATE PROFESSOR, 生物科学系, 助教授 (40192679)

Project Period (FY) 1997 – 2000
KeywordsGTP-binding protein / vesicular transport / ARF / guanine nucleotide exchange factor / GGA protein / dynamin / endocytosis
Research Abstract

Intracellular transport of secretory, membrane and lysosomal proteins is mediated by carrier vesicles, which bud from a donor compartment and fuse with a target compartment to deliver cargo proteins. In the process of vesicle budding, a variety of GTP-binding proteins are involved. In this research project, we have studied on the ARF family of small GTP-binding proteins, their guanine nucleotide exchange factors and their effectors, and a high molecular weight GTP-binding protein, dynamin, and its homolog. We have revealed the followings.
(1). We have identified three guanine nucleotide exchange factors for ARFs, designated BIG1, BIG2 and GBF1, which catalyze the exchange of GDP for GTP on ARFs. All the proteins have a Sec7 domain in their central region, which is essential for the guanine nucleotide exchange activity. We have shown that GBF1 is involved in the formation of COPI-coated vesicles from the cis-Golgi network and BIG2 in the formation of clathrin/AP-1-coated vesicles from the trans-Golgi network.
(2). We have identified a novel family of ARF effectors, designated GGA1, GGA2 and GGA3. All the proteins have a VHS domain, GGAH domain, proline-rich region and an AGEH domain. We have found that, among these domains, the GGAH domain is involved in binding to GTP-bound active ARFs and the AGEH domain in binding to Rabaptin-5 and γ-synergin. Further, we have shown that all the GGA proteins are associated with the trans-Golgi network and regulate the budding of clathrin-coated vesicles.
(3). Dynamin II has been proposed to be involved in the formation of vesicles not only from the plasma membrane but also from the trans-Golgi network. However, by analysis using dynamin mutants, we have shown that dynamin II is not involved in the formation of vesicles from the trans-Golgi network.
(4). We have identified a novel dynamin homolog, designated DVLP, and found that it forms a tetramer by virtue of intramolecular and intermolecular interactions.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Duguay,S.J., et al.: "Processing of wild-type and mutant proinsulin-like growth factor-IA by subtilisinrelated proprotein convertases."J.Biol.Chem.. 272. 6663-6670 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Torii,S., et al.: "Regulation of association of a 58-kDa peripheral membrane protein (58K) with the Golgi apparatus : its membrane binding properties related to but distinct from those of COP I coat proteins."Biomed.Res.. 18. 37-47 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka,S., et al.: "Proteolytic processing of proopiomelanocortin occurs in acidifying secretory granules of AtT-20 cells."J.Histochem.Cytochem.. 45. 425-436 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin,H.-W., et al.: "Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p."J.Biochem.. 122. 525-530 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Li,M., et al.: "Testis-specific prohormone convertase PC4 processes the precursor of pituitary adenylate cyclase-activating polypeptide (PACAP)."Peptides. 19. 259-268 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takatsu,H., et al.: "Identification and characterization of novel clathrin adaptor-related proteins."J.Biol.Chem.. 273. 24693-24700 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamaguchi,T., et al.: "ADP-ribosylation factor-1 is sensitive to N-ethylmaleimide."J.Biochem.. 124. 1229-1236 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toda,K., et al.: "Colocalization of phospholipase D1 and GTP-binding-defective mutant of ADP-ribosylation factor 6 to endosomes and lysosomes."FEBS Lett.. 442. 221-225 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin,H.-W., et al.: "Intermolecular and interdomain interactions of a dynamin-related GTP-binding protein, Dnm1p/Vps1p-like protein."J.Biol.Chem.. 274. 2780-2785 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kasai,K., et al.: "Dynamin II is involved in endocytosis but not in the formation of transport vesicles from the trans-Golgi network."J.Biochem.. 125. 780-789 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Honda,A., et al.: "Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation."Cell. 99. 521-532 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe,Y., et al.: "Subtype-specific trafficking of endothelin receptors."J.Biol.Chem.. 275. 8664-8671 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takatsu,H., et al.: "Adaptor γ ear homology domain conserved in γ-adaptin and GGA proteins that interact with γ-synergin."Biochem.Biophys.Res.Commun.. 271. 719-725 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Futatsumori,M., et al.: "Identification and characterization of novel isoforms of COP I subunits."J.Biochem.. 128. 793-801 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Duguay, S.J., Milewski, W.M., Young, B.D., Nakayama, K.& Steiner D.F.: "Processing of wild-type and mutant proinsulin-like growth factor-IA by subtilisin-related proprotein convertases."J.Biol.Chem.. 272. 6663-6670 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Torii, S., Murakami, K.& Nakayama, K.: "Regulation of association of a 58-kDa peripheral membrane protein (58K) with the Golgi apparatus : its membrane binding properties related to but distinct from those of COP I coat proteins."Biomed.Res.. 18. 37-47 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, S., Yora, T., Nakayama, K., Inoue, K.& Kurosumi, K.: "Proteolytic processing of proopiomelanocortin occurs in acidifying secretory granules of AtT-20 cells."J.Histochem.Cytochem.. 45. 425-436 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin, H.-W., Shinotsuka, C., Torii, S., Murakami, K.& Nakayama, K.: "Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p."J.Biochem.. 122. 525-530 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Li, M., Nakayama, K., Shuto, Y., Somogyvari-Vigh, A.& Arimura, A.: "Testis-specific prohormone convertase PC4 processes the precursor of pituitary adenylate cyclase-activating polypeptide (PACAP)."Peptides. 19. 259-268 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takatsu, H., Sakurai, M., Shin, H.-W., Murakami, K.& Nakayama, K.: "Identification and characterization of novel clathrin adaptor-related proteins."J.Biol.Chem.. 273. 24693-24700 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamaguchi, T., Nakayama, K., Hatsuzawa, K., Tani, K., Himeno, M.& Tagaya, M.: "ADP-ribosylation factor-1 is sensitive to N-ethylmaleimide."J.Biochem.. 124. 1229-1236 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toda, K., Nogami, M., Murakami, K., Kanaho, Y.& Nakayama, K.: "Colocalization of phospholipase D1 and GTP-binding-defective mutant of ADP-ribosylation factor 6 to endosomes and lysosomes."FEBS Lett.. 442. 221-225 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin, H.-W., Takatsu, H., Mukai, H., Munekata, E., Murakami, K.& Nakayama, K.: "Intermolecular and interdomain interactions of a dynamin-related GTP-binding protein, Dnm1p/Vps1p-like protein."J.Biol.Chem.. 274. 2780-2785 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kasai, K., Shin, H.-W., Shinotsuka, C., Murakami, K.& Nakayama, K.: "Dynamin II is involved in endocytosis but not in the formation of transport vesicles from the trasn-Golgi network."J.Biochem.. 125. 780-789 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Honda, A., Nogami, M., Yokozeki, T., Yamazaki, M., Nakamura, H., Watanabe, H., Kawamoto, K., Nakayama, K., Morris, A.J., Frohman, M.A.& Kanaho, Y.: "Phosphatidylinositol 4-phosphate 5-kinase α is a downstream effector of the small G protein ARF6 in membrane ruffle formation."Cell. 99. 521-532 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe, Y., Nakayama, K., Yamanaka, A., Sakurai, T.& Goto, K.: "Subtype-specific trafficking of endothelin receptors."J.Biol.Chem.. 275. 8664-8671 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takatsu, H., Yoshino, K.& Nakayama, K.: "Adaptor γ ear homology domain conserved in γ-adaptin and GGA proteins that interact with γ-synergin."Biochem.Biophys.Res.Commun.. 271. 719-725 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Futatsumori, M., Kasai, K., Takatsu, H., Shin, H.-W.& Nakayama, K.: "Identification and characterization of novel isoforms of COP I subunits."J.Biochem.. 128. 793-801 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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