Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis.
The human fungal pathogen Candida albicans switches from yeast to hyphal growth when exposed to serum or phagocytosed. However, the importance of this morphological switch for virulence remains highly controversial due to the lack of a mutant that affects hyphal morphogenesis only. Although many genes specifically expressed in hyphal cells have been identified and shown to encode virulence factors, none is required for hyphal morphogenesis. Here we report the first hypha-specific gene identified, HGC1, which is essential for hyphal morphogenesis. Deletion of HGC1 abolished hyphal growth in all laboratory conditions tested and in the kidneys of systemically infected mice with markedly reduced virulence. HGC1 expression is co-regulated with other virulence genes such as HWP1 by the cAMP/protein kinase A signaling pathway and transcriptional repressor Tup1/Nrg1. Hgc1 is a G1 cyclin-related protein and co-precipitated with the cyclin-dependent kinase (Cdk) CaCdc28. It has recently emerged that cyclin/Cdk complexes promote other forms of polarized cell growth such as tumor cell migration and neurite outgrowth. C. albicans seems to have adapted a conserved strategy to control specifically hyphal morphogenesis.
Zheng
Xinde
X
Institute of Molecular and Cell Biology, Singapore, Singapore.
Wang
Yanming
Y
Wang
Yue
Y
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010641:Phenotype; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D015996:Survival Rate; D014774:Virulence
D000199:Actins; C534702:CCNG1 protein, human; C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; C082909:ECE1 protein, Candida albicans; D005656:Fungal Proteins; C118102:HWP1 protein, Candida albicans; C101636:HYR1 protein, Candida albicans; D008562:Membrane Glycoproteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D042846:CDC2-CDC28 Kinases