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The NDR Kinase Cbk1 Downregulates the Transcriptional Repressor Nrg1 through the mRNA-Binding Protein Ssd1 in Candida

Hye-Jeong Lee1, Jong-Myeong Kim1, Woo Kyu Kang1

  • 1Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.

Eukaryotic Cell
|May 24, 2015
PubMed

Insights

Nuclear Dbf2-related (NDR) kinase Cbk1 regulates Candida albicans hyphal growth by downregulating the repressor Nrg1 via the Ssd1 protein. Ssd1 phosphorylation by Cbk1 is crucial for this process and hyphal development.

Area of Science:

  • Molecular Biology
  • Mycology
  • Cell Biology

Background:

  • Nuclear Dbf2-related (NDR) kinases are vital for cellular processes.
  • Cbk1, an NDR kinase, is essential for Candida albicans hyphal growth, but its precise functions remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Cbk1 regulates hyphal morphogenesis in Candida albicans.
  • To investigate the role of the mRNA-binding protein Ssd1 in Cbk1-mediated hyphal development.

Main Methods:

  • Investigated the interaction between Cbk1 and Ssd1 using genetic and biochemical approaches.
  • Analyzed the localization of Ssd1 in C. albicans mutants.
  • Utilized phosphomimetic and phosphodeficient Ssd1 alleles to assess the role of phosphorylation.
  • Examined the expression of transcriptional repressor Nrg1 and Als3 in various mutant strains.
  • Assessed fungal internalization in human cell lines.

Main Results:

  • Cbk1 downregulates the transcriptional repressor Nrg1 through Ssd1, which contains Cbk1 phosphorylation sites.
  • Deletion of SSD1 partially rescued the hyphal growth defect of cbk1Δ/Δ mutants.
  • Cbk1 is required for Ssd1 localization to polarized growth sites.
  • Phosphorylation of Ssd1 by Cbk1 is critical for hyphal morphogenesis.
  • Nrg1 is not downregulated in cbk1Δ/Δ mutants but is absent in cbk1Δ/Δ ssd1Δ/Δ double mutants.
  • SSD1 deletion enhanced Als3 expression and fungal internalization in HEK293T cells.

Conclusions:

  • Cbk1 regulates Nrg1 downregulation via Ssd1, a key mechanism for Candida albicans hyphal morphogenesis.
  • Ssd1 phosphorylation by Cbk1 is essential for proper hyphal development and virulence factor expression.

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