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Studies on signal transduction pathway, which affect virulence of Candida albicans

Research Project

Project/Area Number 15580062
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied microbiology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

TAMAKI Hisanori  KYOTO UNIVERSITY, GRADUATE SCHOOL OF BIOSTUDIES, INSTRUCTOR, 生命科学研究科, 助手 (20212045)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsCandida albicans / Infectious disease / Morphogenesis / Receptor / G-protein / Signal transduction
Research Abstract

In response to various extracellular signals, the morphology of the human fungal pathogen Candida albicans switches from yeast to hyphal form. Here, we report that GPR1 encoding a putative G-protein coupled receptor and GPA2 encoding a Gα subunit are required for hyphal formation and morphogenesis in C.albicans. Mutants lacking Gpr1(gpr1/gpr1) or Gpa2(gpa2/gpa2) are defective in hyphal formation and morphogenesis on solid hyphal-inducing media. These phenotypic defects in solid cultures are suppressed by exogenously added dibutyryl-cAMP. Biochemical studies also reveal that GPR1 and GPA2 are required for a glucose-dependent increase in cellular cAMP. An epistasis analysis indicates that Gpr1 functions upstream of Gpa2 in the same signaling pathway, and a two-hybrid assay reveals that the carboxyl terminal tail of Gpr1 interacts with Gpa2. Moreover, expression levels of HWP1 and ECE1, which are cAMP-dependent hyphal-specific genes, are reduced in both mutant strains. These findings support a model that Gpr1 as well as Gpa2 regulates hyphal formation and morphogenesis in a cAMP-dependent manner. In contrast, GPR1 and GPA2 are not required for hyphal formation in liquid FBS medium. Furthermore, the gpr1l and the gpa2 mutant strains are fully virulent in a mouse infection. These findings suggest that Gpr1 and Gpa2 are involved in the glucose sensing machinery that regulates morphogenesis and hyphal formation in solid media via a cAMP-dependent mechanism, but they are not required for hyphal formation in liquid medium or during invasive candidiasis.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (4 results)

All 2005 2004 Other

All Journal Article (3 results) Publications (1 results)

  • [Journal Article] Glucose-dependent cell size is regulated by a G protein-coupled receptor system in yeast Saccharomyces cerevisiae.2005

    • Author(s)
      H.Tamaki, C.-W.Yun, et al.
    • Journal Title

      Genes Cells 10・(3)

      Pages: 193-206

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus Candida albicans2004

    • Author(s)
      T.Miwa, Y.Takagi, H.Tamaki et al.
    • Journal Title

      Eukaryot.Cell 3・(4)

      Pages: 919-931

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus Candida albicans.2004

    • Author(s)
      T.Miwa, Y.Takagi, H.Tamaki et al.
    • Journal Title

      Eukaryot.Cell 3・(4)

      Pages: 919-931

    • Related Report
      2004 Annual Research Report
  • [Publications] Kato, T., Mizutani, T., Tamaki, H., et al.: "Characterization of heterotrimeric G protein complexes in rice plasma membrane"Plant J.. (in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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