A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Hyphal Development
Candida albicans is a major fungal pathogen in immunologically compromised patients. A key virulence trait is its ability to switch between the yeast and hyphal forms. Whereas yeast cells are required for dissemination, the filamentous forms are important in tissue penetration and invasion. In order to make a hypha, cell separation must be inhibited after cytokinesis, although the full extent of its regulation remains unknown. Previously, we have shown that the inhibition of cell separation in hyphae requires a modification of the dynamic properties of septins, a conserved family of GTPases that normally form a ring at the site of cytokinesis. Here we describe new factors regulating septin dynamics during hyphal development. We have discovered that an alternative translation initiation of ACE2 mRNAs gives rise to an Ace2 protein, Ace2L, with an extra 54 aa at the N-terminus that exhibits a localization and function different from Ace2 transcription factor. This Ace2L protein is upregulated upon hyphal induction and regulates the incorporation of the Sep7 septin into the septin rings to avoid inappropriate activation of cell separation in hyphae. Finally, we present evidence suggesting that the NDR kinase Cbk1 interacts with Ace2L to regulate this process.
Vyšlo v časopise:
A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Hyphal Development. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005152
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005152
Souhrn
Candida albicans is a major fungal pathogen in immunologically compromised patients. A key virulence trait is its ability to switch between the yeast and hyphal forms. Whereas yeast cells are required for dissemination, the filamentous forms are important in tissue penetration and invasion. In order to make a hypha, cell separation must be inhibited after cytokinesis, although the full extent of its regulation remains unknown. Previously, we have shown that the inhibition of cell separation in hyphae requires a modification of the dynamic properties of septins, a conserved family of GTPases that normally form a ring at the site of cytokinesis. Here we describe new factors regulating septin dynamics during hyphal development. We have discovered that an alternative translation initiation of ACE2 mRNAs gives rise to an Ace2 protein, Ace2L, with an extra 54 aa at the N-terminus that exhibits a localization and function different from Ace2 transcription factor. This Ace2L protein is upregulated upon hyphal induction and regulates the incorporation of the Sep7 septin into the septin rings to avoid inappropriate activation of cell separation in hyphae. Finally, we present evidence suggesting that the NDR kinase Cbk1 interacts with Ace2L to regulate this process.
Zdroje
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