The Unfolded Protein Response Regulates Pathogenic Development of Ustilago maydis by Rok1-Dependent Inhibition of Mating-Type Signaling.

Fungal pathogens require the unfolded protein response (UPR) to maintain protein homeostasis of the endoplasmic reticulum (ER) during pathogenic development. In the corn smut fungus , pathogenic development is controlled by the and mating-type loci. The UPR is specifically activated after plant penetration and required for efficient secretion of effectors and suppression of the plant defense response. The interaction between the UPR regulator Cib1 and the central developmental regulator Clp1 modulates the pathogenic program and triggers fungal colonization of the host plant. By contrast, when activated before plant penetration, the UPR interferes with fungal virulence by reducing expression of and , the central regulators of pathogenic development encoded by the mating-type locus. Here, we show that this inhibitory effect results from UPR-mediated suppression of the pheromone response pathway upstream of the b regulatory network. UPR activity prompts dephosphorylation of the pheromone-responsive mitogen-activated protein kinase (MAPK) Kpp2, reducing activity of the pheromone response factor Prf1 that regulates expression of and Deletion of the dual specificity phosphatase fully suppressed UPR-dependent inhibition of Kpp2 phosphorylation, formation of infectious filaments, and fungal virulence. Rok1 determines the activity of mating-type signaling pathways and thus the degree of fungal virulence. We propose that UPR-dependent regulation of Rok1 aligns ER physiology with fungal aggressiveness and effector gene expression during biotrophic growth of in the host plant. The unfolded protein response (UPR) is crucial for endoplasmic reticulum (ER) homeostasis and disease development in fungal pathogens. In the plant-pathogenic fungus , the UPR supports fungal proliferation and effector secretion for plant defense suppression. In this study, we uncovered that UPR activity, which is normally restricted to the biotrophic stage , inhibits mating and the formation of infectious filaments by Rok1-dependent dephosphorylation of the pheromone responsive mitogen-activated protein kinase (MAPK) Kpp2. This observation is relevant for understanding how the fungal virulence program is regulated by cellular physiology. UPR-mediated control of mating-type signaling pathways predicts that effector gene expression and the virulence potential are controlled by ER stress levels.