The serine/threonine protein phosphatase SIT4 modulates yeast-to-hypha morphogenesis and virulence in Candida albicans.
SIT4 encodes the multifunctional catalytic subunit of a type 2A-related protein phosphatase of Saccharomyces cerevisiae and has been implicated in cell cycle regulation and nitrogen sensing. We have identified the Candida albicans homologue of SIT4, and we show that its disruption caused a significant reduction in general growth rate, in hyphal outgrowth and in virulence in a mouse infection model. These phenotypes were reversed by the reintroduction of the wild-type SIT4 gene. We used glass DNA microarrays to measure the transcriptional profiles of 6287 open reading frames in sit4 cells undergoing the yeast-to-hypha transition induced by serum. Although differential expression of many of the hyphae-specific genes was not affected by the SIT4 deletion, the transcription of two new hyphae-induced genes, XOG1 and YNR67, was entirely reliant upon Sit4p. Both genes represent glucanases, indicating that SIT4 may play a role in controlling cell wall biogenesis. Furthermore, sit4 cells exhibited a reduced heat shock response to treatment with serum/37 degrees C, suggesting that SIT4 acts to co-ordinate the stress response signals during morphological switching. Finally, sit4 cells displayed reduced transcript levels for the genes encoding the Hog1p MAP kinase and several modulators of protein biosynthesis. Sit4p thus plays important roles during hyphal growth in Candida albicans through the regulation of cell wall biogenesis, osmosensing and protein translation.
Lee
Chang-Muk
CM
Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montréal, Quebec H4P 2R2, Canada.
Nantel
André
A
Jiang
Linghuo
L
Whiteway
Malcolm
M
Shen
Shi-Hsiang
SH
D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D002177:Candidiasis / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009024:Morphogenesis; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2; D029701:Saccharomyces cerevisiae Proteins; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D037521:Virulence Factors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C104343:SIT4 protein, S cerevisiae