Role of the unfolded protein response in development and pathogenicity of Ustilago maydis

• Applicant: Professor Dr. Kai Heimel
• Subject Area: Plant Genetics and Genomics
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 262636951

The unfolded protein response (UPR), a highly conserved eukaryotic signaling pathway, primarily serves to ensure homeostasis of the endoplasmic reticulum (ER) during situations of increased demands on the secretory system. Recent studies revealed that the UPR is also involved in controlling development and differentiation in eukaryotes. However, the molecular mechanisms underlying UPR-dependent developmental control in higher eukaryotes are poorly understood and even less is known in fungi. Previous studies in the phytopathogenic fungus Ustilago maydis revealed crosstalk between the UPR and the developmental control pathway on multiple levels. The link between the UPR and developmental control is accomplished via direct interaction between the central UPR regulator Cib1 and Clp1, an essential factor of developmental control. This interaction leads to stabilization of Clp1 and increased ER stress resistance. As Clp1 controls fungal proliferation in planta, Clp1/Cib1 complex formation promotes developmental progression and prevents UPR hyperactivation at the onset of and during biotrophic development, respectively. Conversely, premature UPR activation interferes with the morphogenetic switch from budding to infectious filamentous growth, independent of Clp1. We will use a combination of transcriptomics, cell biological and biochemical approaches to study the mechanisms of Clp1-dependent and Clp1-independent interplay between the UPR and developmental control pathways. In a second project we will investigate the consequences of UPR hyperactivation. Of special interest will be the functional analysis of a UPR repressor encoded by the unspliced mRNA of a Hac1/Xbp1 homolog that prevents deleterious UPR hyperactivation and affects fine-tuning of UPR activity. This function is novel for fungi but strikingly similar to the situation in higher eukaryotes. U. maydis serves as a simple but powerful genetic model system to investigate the specific protein functions in vivo. Our studies are of particular interest with respect to UPR-dependent disease development in higher eukaryotes, since UPR hyperactivation has fatal consequences in both, fungi and humans.

• DFG Programme: Research Grants