Cyclin Cln3p Links G1 Progression to Hyphal and Pseudohyphal Development in Candida albicans

摘要

G₁ cyclins coordinate environmental conditions with growth and differentiation in many organisms. In the pathogen Candida albicans, differentiation of hyphae is induced by environmental cues but in a cell cycle-independent manner. Intriguingly, repressing the G₁ cyclin Cln3p under yeast growth conditions caused yeast cells to arrest in G₁, increase in size, and then develop into hyphae and pseudohyphae, which subsequently resumed the cell cycle. Differentiation was dependent on Efg1p, Cph1p, and Ras1p, but absence of Ras1p was also synthetically lethal with repression of CLN3. In contrast, repressing CLN3 in environment-induced hyphae did not inhibit growth or the cell cycle, suggesting that yeast and hyphal cell cycles may be regulated differently. Therefore, absence of a G₁ cyclin can activate developmental pathways in C. albicans and uncouple differentiation from the normal environmental controls. The data suggest that the G₁ phase of the cell cycle may therefore play a critical role in regulating hyphal and pseudohyphal development in C. albicans.