Unfolded Protein Response (UPR) Regulator Cib1 Controls Expression of Genes Encoding Secreted Virulence Factors in Ustilago maydis.
The unfolded protein response (UPR), a conserved eukaryotic signaling pathway to ensure protein homeostasis in the endoplasmic reticulum (ER), coordinates biotrophic development in the corn smut fungus Ustilago maydis. Exact timing of UPR activation is required for virulence and presumably connected to the elevated expression of secreted effector proteins during infection of the host plant Zea mays. In the baker's yeast Saccharomyces cerevisiae, expression of UPR target genes is induced upon binding of the central regulator Hac1 to unfolded protein response elements (UPREs) in their promoters. While a role of the UPR in effector secretion has been described previously, we investigated a potential UPR-dependent regulation of genes encoding secreted effector proteins. In silico prediction of UPREs in promoter regions identified the previously characterized effector genes pit2 and tin1-1, as bona fide UPR target genes. Furthermore, direct binding of the Hac1-homolog Cib1 to the UPRE containing promoter fragments of both genes was confirmed by quantitative chromatin immunoprecipitation (qChIP) analysis. Targeted deletion of the UPRE abolished Cib1-dependent expression of pit2 and significantly affected virulence. Furthermore, ER stress strongly increased Pit2 expression and secretion. This study expands the role of the UPR as a signal hub in fungal virulence and illustrates, how biotrophic fungi can coordinate cellular physiology, development and regulation of secreted virulence factors.
Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Göttingen, Germany.|Center for Molecular Biosciences (GZMB), Georg-August-University, Göttingen, Germany.
Martin
M
Hampel
Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Göttingen, Germany.
Mareike
M
Jakobi
Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Göttingen, Germany.
Lara
L
Schmitz
Botanical Institute and Cluster of Excellence on Plant Sciences, University of Cologne, Cologne Germany.
Ute
U
Meyer
Institute of Molecular Biology and Tumor Research (IMT), Philipps-University, Marburg, Germany.
Florian
F
Finkernagel
Botanical Institute and Cluster of Excellence on Plant Sciences, University of Cologne, Cologne Germany.
Gunther
G
Doehlemann
Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Göttingen, Germany.|Center for Molecular Biosciences (GZMB), Georg-August-University, Göttingen, Germany.
Kai
K
Heimel
D004721:Endoplasmic Reticulum / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017510:Protein Folding; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D056811:Unfolded Protein Response / Q000235:genetics*; D014588:Ustilago / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics*; D003313:Zea mays / Q000235:genetics / Q000382:microbiology
D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D037521:Virulence Factors