Possible integration of upstream signals at Cdc42 in filamentous differentiation of S. cerevisiae

Various environmental stimuli (such as nitrogen starvation, short-chain alcohols and slowed DNA synthesis) induce filamentous differentiation in S. cerevisiae. Genetic mutations (such as deletion of the mitotic cyclin gene CLB2) cause constitutive filamentous differentiation. Although different stimulus-induced filamentous differentiation involves different signalling pathways, Cdc42 has been identified as a common regulator. We show here that Cdc42 is also required for hydroxyurea (HU)-induced and clb2Δ-caused filamentous growth. We show that the mitotic CDK Clb2/Cdc28 functions upstream of Cdc42 in regulating filamentous differentiation. This result points to possible existence of a Cdc42-MAPK-Clb2/Cdc28 positive feedback loop in the signalling of filamentous differentiation. We report isolation of a cdc42-Y40F allele that blocks HU-induced, but not nitrogen starvation-induced, short-chain alcohol-induced or clb2Δ-caused, filamentation. Based on these results, we propose a model in which Cdc42 functions as a possible integrator for the upstream signals of filamentous differentiation (from the filamentous growth MAPK pathway, the cAMP pathway and the Mec1/Rad53 checkpoint pathway). We also show evidence that the mitotic CDK inhibitor Swe1 may mediate the cross-talk between the cAMP and MAPK pathways.