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BASIC RESEARCH TO EXPLOIT PROPERTIES OF ENDOTHELIAL CAVEOLAE FOR DEVELOPMENT OF PREVENTIVE AND/OR TREATING MEASURES FOR VASCULAR DISEASES

Research Project

Project/Area Number 09557001
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General anatomy (including Histology/Embryology)
Research InstitutionNAGOYA UNIVERSITY (1999)
Gunma University (1997-1998)

Principal Investigator

FUJIMOTO Toyoshi  NAGOYA UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50115929)

Co-Investigator(Kenkyū-buntansha) TERASHITA Zen-chi  TAKEDA PHARM. CO., RESEARCH INST., PRESIDENT, 創薬研究所III, 所長
KOGO Hiroshi  SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (20282387)
HAGIWARA Haruo  GUNMA UNIV., SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (80189464)
青木 武生  , 助手 (70150919)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥6,800,000 (Direct Cost: ¥6,800,000)
KeywordsCAVEOLA / ENDOPLASMIC RETICULUM / CALCIUM / CAVEOLIN-1 / TYROSINE PHOSPHORYLATION / ISOFORM / 内皮細胞 / アリソフォーム / 細胞膜 / タイムラプス法
Research Abstract

Caveolae are small invaginations of the plasma membrane found in many cell types, and caveolins (caveolin-1,2,3) are a family of integral membrane proteins forming the framework of caveolae. Caveolae and caveolins have been revealed to have diverse functions, including endocytosis, signal transduction, cholesterol transport, and tumor suppression. To understand caveolae and caveolins in molecular terms, we have done several lines of research using various cell biological techniques.
Caveolin-1 is heavily phosphorylated in tyrosine in v-Src-expressing cells, but consequences of the phosphorylation has not been known. We generated a polyclonal antibody specific for tyrosine-phosphorylated caveolin-1 (PY14). In v-Src-expressing cells, PY14 labeled caveolae, flat plasmalemmal areas of various sizes and shapes, and intracellular vesicles that are significantly larger than caveolae ; biochemical properties of caveolin-1, including detergent insolubility and oligomerization, were not different from the non-phosphorylated counterpart. In normal rat tissues in vivo, the endothelium of the continuous capillary was labeled by PY14, whereas the endothelium of other vessels was not. In the cultured endothelium, tyrosine phosphatase inhibitors as well as oxidative stress induced tyrosine phosphorylation of caveolin-1, and caused vesiculation of caveolae. These results suggest that tyrosine phosphorylation of caveolin-1 induces vesiculation and/or aggregation of caveolae.
We used freeze-fracture immunoelectron microscopy to examine distribution of the two isoforms (α, β) of caveolin-1. Antibodies specific to the α isoform decorated deep caveolae preferentially, whereas those reacting with both α and β isoforms labeled deep and shallow caveolae with similar efficiency. The result indicates that the α/β ratio is different among caveolae, and may suggest that caveolae of different depths is not be convertible each other.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Fujimoto T.: "C-linked plasmalemmal cholesterol is sequestered to caveolae : analysis with a new cytochemical probe"J. Histochem. Cytochem.. 45. 1197-1205 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura R.: "Two-dimensional distribution of Gi2α in the plasma membrane : a critical evoluation by immunocytochemistry"FEBS Lett.. 415. 139-144 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kogo H.: "Caveolae and endoplasmic reticulum : immunofluorescence microscopy and time laspe analysis"Acta Histochem. Cytochem.. 30. 593-599 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isshiki M.: "Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges"Proc. Natl. Acad. Sci. USA. 95. 5009-5014 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura R.: "Tyrosine phosphorylated caveolin-1 : immunolocalization and molecular characterization"Mol. Biol. Cell. 10. 975-986 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Aoki T.: "Tyrosine phosphorylation of caveolin-1 in the endothelium"Exp. Cell Res.. 253. 629-636 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujimoto, T. M. Hayashi, M. Iwamoto and Y. Ohno-Iwashita: "Cross-linked plasmalemmal cholesterol is sequestered to caveolae : analysis with a new cytochemical probe"J. Histochem. Cytochem. 45. 1197-1205 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura, R., C. Inuo, Y. Takahashi, T. Asano, and T. Fujimoto: "Two-dimensional distribution of Gi2α in the plasma membrane : a critical evaluation by immuno-cytochemistry"FEBS Lett.. 415. 139-144 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kogo, H., M. Shioya, Y. Takahashi, and T. Fujimoto: "Caveolae and endoplasmic reticulum : immuno-fluorescence microscopy and time lapse analysis"Acta Histochem Cytochem. 30. 593-599 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isshiki, M., J. Ando, R. Korenaga, H. Kogo, T. Fujimoto, T. Fujita, and A. Kamiya: "Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges"Proc. Natl. Acad. Sci. USA. 95. 5009-5014 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nomura, R., and T. Fujimoto: "Tyrosine phosphorylated caveolin-1 : immunolocalization and molecular characterization"Mol. Biol. Cell. 10. 975-986 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Aoki, T., R. Nomura, and T. Fujimoto: "Tyrosine phosphorylation of caveolin-1 in the endothelium"Exp. Cell Res.. 253. 629-636 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hagiwara H.: "Cross-linking of plasmalemmal cholesterol in lymphocytes induces capping,membrane shedding,and endocytosis through coated pits"Biochem.Biophys.Res.Commun.. 260. 516-521 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kogo H.: "Caveolin-1 isoforms are encoded by distinct mRNAs.Identification of mouse caveolin-1 mRNA variants caused by alternative transcription initiation and splicing."FEBS lett.. 465. 119-123 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 藤本豊士: "カベオラと形質膜の機能ドメイン"膜(membrane). 24. 2-8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Isshiki,M.,J.Ando,R.Kounaga,H.Kogo,T.Fujimoto,T.Fujita,and A.Komiya: "Endothelial Ca^<2+> waves preferentially originate at specific loci in Caveolin-rich cell edges" Proc.Natll.Acad.Sci.USA. 95. 5009-5014 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujimoto,T.,H.Hagiwara,T.Aoki H.Kogo and R.Nomura: "Cavealse:from a morphological point of view." J.Electron Microsc.47. 451-460 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,R.,and Fujimoto: "Jyrosine phosphorylated caveolin-1:immunolocalization and molecular characterization" Mol.Biol.Cell.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,R., C.Inuo, Y.Takahashi.T.Asano, and T.Fujimoto: "Two-dimensional distribution of Gi2a in the plasma memlrane:a critical evalustion by immunocytahemistry" FEBS.Lett. 415. 139-144 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kogo,H., M.Shioya, Y.Takahashi, and T.Fujimoto: "Caveolae and endoplasmic reticulum:immunoqeuorescence microscopy and time lapse analysis." Acta Histochem.Cytochem.30. 593-599 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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