Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent hyphal-like growth.
Morphogenesis in the fungal pathogen Candida albicans is an important virulence-determining factor, as a dimorphic switch between yeast and hyphal growth forms can increase pathogenesis. We identified CaCDC5, a cell cycle regulatory polo-like kinase (PLK) in C. albicans and demonstrate that shutting off its expression induced cell cycle defects and dramatic changes in morphology. Cells lacking CaCdc5p were blocked early in nuclear division with very short spindles and unseparated chromatin. GFP-tagged CaCdc5p localized to unseparated spindle pole bodies, the spindle, and chromatin, consistent with a role in spindle elongation at an earlier point in the cell cycle than that described for the homologue Cdc5p in yeast. Strikingly, the cell cycle defects were accompanied by the formation of hyphal-like filaments under yeast growth conditions. Filament growth was determinate, as the filaments started to die after 24 h. The filaments resembled serum-induced hyphae with respect to morphology, organization of cytoplasmic microtubules, localization of nuclei, and expression of hyphal-specific components. Filament formation required CaCDC35, but not EFG1 or CPH1. Similar defects in spindle elongation and a corresponding induction of filaments occurred when yeast cells were exposed to hydroxyurea. Because CaCdc5p does not appear to act as a direct repressor of hyphal growth, the data suggest that a target of CaCdc5p function is associated with hyphal-like development. Thus, an internal, cell cycle-related cue can activate hyphal regulatory networks in Candida.
Bachewich
Catherine
C
Health Sector, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, H4P 2R2, Canada. catherine.bachewich@nrc.ca
Thomas
David Y
DY
Whiteway
Malcolm
M
D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D018797:Cell Cycle Proteins; D006918:Hydroxyurea / Q000494:pharmacology; D025301:Hyphae / Q000201:enzymology* / Q000254:growth & development; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism
D018797:Cell Cycle Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae; D006918:Hydroxyurea