New Aspects of Invasive Growth Regulation Identified by Functional Profiling of MAPK Pathway Targets in Saccharomyces cerevisiae

• Published in: Genetics (Austin) Vol. 216; no. 1; pp. 95 - 116
• Main Authors: Vandermeulen, Matthew D, Cullen, Paul J
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-09-2020; Genetics Society of America
• Subjects: Adhesion; Amino acids; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell adhesion; Cell adhesion & migration; Cell cycle; Cell Division - genetics; Cell morphology; Cytology; Eukaryotes; Functional analysis; Fungi; Gene expression; Genes; Genetics; Genotype & phenotype; Glycoproteins - genetics; Glycoproteins - metabolism; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Investigations; Kinases; MAP kinase; MAP Kinase Signaling System; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Morphogenesis; Morphology; Proteins; Regulatory proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; Roles; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal transduction; Target recognition; Transcription factors; Yeast; Yeasts; filamentous growth; adhesion; transcription; fungal pathogens; expression profiling
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.120.303369

Abstract
MAPK pathways are universal regulators of morphogenesis and stress responses in eukaryotes. In this study, Vandermeulen and Cullen identified the function of transcriptional targets of a MAPK pathway in yeast...
Abstract
MAPK pathways are drivers of morphogenesis and stress responses in eukaryotes. A major function of MAPK pathways is the transcriptional induction of target genes, which produce proteins that collectively generate a cellular response. One approach to comprehensively understand how MAPK pathways regulate cellular responses is to characterize the individual functions of their transcriptional targets. Here, by examining uncharacterized targets of the MAPK pathway that positively regulates filamentous growth in Saccharomyces cerevisiae (fMAPK pathway), we identified a new role for the pathway in negatively regulating invasive growth. Specifically, four targets were identified that had an inhibitory role in invasive growth: RPI1, RGD2, TIP1, and NFG1/YLR042c. NFG1 was a highly induced unknown open reading frame that negatively regulated the filamentous growth MAPK pathway. We also identified SFG1, which encodes a transcription factor, as a target of the fMAPK pathway. Sfg1p promoted cell adhesion independently from the fMAPK pathway target and major cell adhesion flocculin Flo11p, by repressing genes encoding presumptive cell-wall-degrading enzymes. Sfg1p also contributed to FLO11 expression. Sfg1p and Flo11p regulated different aspects of cell adhesion, and their roles varied based on the environment. Sfg1p also induced an elongated cell morphology, presumably through a cell-cycle delay. Thus, the fMAPK pathway coordinates positive and negative regulatory proteins to fine-tune filamentous growth resulting in a nuanced response. Functional analysis of other pathways’ targets may lead to a more comprehensive understanding of how signaling cascades generate biological responses.