The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in <i>Saccharomyces cerevisiae</i>

Karunanithi, Sellam; Cullen, Paul J.

doi:10.1534/genetics.112.142661

Cited by 52 publications

(66 citation statements)

References 146 publications

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“…A PCR fragment containing 600 bp of the CDC24 promoter was amplified with 5= BamHI and 3= PstI sites and introduced into YEp351. A second fragment was generated by PCR that introduced a myristoylation site (55,163) into the N terminus of Cdc24p. This PCR fragment was generated by amplification of CDC24-GFP from strain PC1205.…”

Section: Methodsmentioning

confidence: 99%

Cdc42p-Interacting Protein Bem4p Regulates the Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

Pitoniak

Chavel

Chow

et al. 2015

Molecular and Cellular Biology

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The ubiquitous Rho (Ras homology) GTPase Cdc42p can function in different settings to regulate cell polarity and cellular signaling. How Cdc42p and other proteins are directed to function in a particular context remains unclear. We show that the Cdc42p-interacting protein Bem4p regulates the mitogen-activated protein kinase (MAPK) pathway that controls filamentous growth in Saccharomyces cerevisiae. Bem4p controlled the filamentous-growth pathway but not other MAPK pathways (mating or high-osmolarity glycerol response [HOG]) that also require Cdc42p and other shared components. Bem4p associated with the plasma membrane (PM) protein, Sho1p, to regulate MAPK activity and cell polarization under nutrient-limiting conditions that favor filamentous growth. Bem4p also interacted with the major activator of Cdc42p, the guanine nucleotide exchange factor (GEF) Cdc24p, which we show also regulates the filamentous-growth pathway. Bem4p interacted with the pleckstrin homology (PH) domain of Cdc24p, which functions in an autoinhibitory capacity, and was required, along with other pathway regulators, to maintain Cdc24p at polarized sites during filamentous growth. Bem4p also interacted with the MAPK kinase kinase (MAPKKK) Ste11p. Thus, Bem4p is a new regulator of the filamentous-growth MAPK pathway and binds to general proteins, like Cdc42p and Ste11p, to promote a pathway-specific response.

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Section: Methodsmentioning

confidence: 99%

Cdc42p-Interacting Protein Bem4p Regulates the Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

Pitoniak

Chavel

Chow

et al. 2015

Molecular and Cellular Biology

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“…For some experiments, the filamentous growth MAPK pathway was evaluated with a growth reporter [FUS1-HIS3, (McCaffrey et al 1987)]. In S1278b cells lacking an intact mating pathway (ste4D), growth on SD-HIS is dependent on the filamentous growth MAPK pathway (O'Rourke and Herskowitz 1998; Cullen et al 2004;Pitoniak et al 2009;Chavel et al 2010;Karunanithi and Cullen 2012). Growth assays are shown in Figure S1.…”

Section: Strains Plasmids and Microbiological Techniquesmentioning

confidence: 99%

“…Cdc24p and Cdc42p are essential proteins and were not tested here, and Ste7p was not present in the collection. Opy2p is an established regulator of the filamentous growth MAPK pathway (Yang et al , 2010Karunanithi and Cullen 2012) and showed a defect in FRE-lacZ expression, but the levels fell below the range of statistical significance (Table S3). (B) Example of the plate-washing assay.…”

Section: Identification Of Filamentous Growth Mapk Pathway Regulatorsmentioning

confidence: 99%

“…MAPK pathways are evolutionary conserved signaling modules that regulate diverse responses in eukaryotes (Raman et al 2007). The filamentous growth MAPK pathway is composed of plasma-membrane sensors (Msb2p, Sho1p, and Opy2p) (O'Rourke and Herskowitz 1998; Cullen et al 2004;Wu et al 2006;Karunanithi and Cullen 2012) that connect to a Rho-type GTPase (Cdc42p; Bi and Park 2012) and a kinase cascade consisting of a p21-activated kinase (Ste20p; Peter et al 1996;Leberer et al 1997) and MAPK module (including the MAPKKK Ste11p, MAPKK Ste7p, and MAPK Kss1p; Roberts and Fink 1994). The MAP kinase Kss1p regulates the activity of two transcription factors (Ste12p and Tec1p; ) that induce target genes ) by binding to well-defined promoter elements (Zeitlinger et al 2003;Chou et al 2006).…”

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confidence: 99%

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Global Regulation of a Differentiation MAPK Pathway in Yeast

Chavel

Caccamise

Li³

et al. 2014

Genetics

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Cell differentiation requires different pathways to act in concert to produce a specialized cell type. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth in response to nutrient limitation. Differentiation to the filamentous cell type requires multiple signaling pathways, including a mitogen-activated protein kinase (MAPK) pathway. To identify new regulators of the filamentous growth MAPK pathway, a genetic screen was performed with a collection of 4072 nonessential deletion mutants constructed in the filamentous (S1278b) strain background. The screen, in combination with directed gene-deletion analysis, uncovered 97 new regulators of the filamentous growth MAPK pathway comprising 40% of the major regulators of filamentous growth. Functional classification extended known connections to the pathway and identified new connections. One function for the extensive regulatory network was to adjust the activity of the filamentous growth MAPK pathway to the activity of other pathways that regulate the response. In support of this idea, an unregulated filamentous growth MAPK pathway led to an uncoordinated response. Many of the pathways that regulate filamentous growth also regulated each other's targets, which brings to light an integrated signaling network that regulates the differentiation response. The regulatory network characterized here provides a template for understanding MAPK-dependent differentiation that may extend to other systems, including fungal pathogens and metazoans.

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“…In contrast, the CR domain seems to be important for activating Hog1 through the SHO1 branch (9). Opy2 is also involved in the filamentous growth Kss1 MAPK pathway, and a point mutation in the Opy2 CR domain (C30Y) reduces the activation of Kss1 by glucose starvation (26). The molecular function of the Opy2 CR domain, however, remains unclear.…”

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confidence: 99%

Binding of the Extracellular Eight-Cysteine Motif of Opy2 to the Putative Osmosensor Msb2 Is Essential for Activation of the Yeast High-Osmolarity Glycerol Pathway

Yamamoto

Tatebayashi

Saito

2016

Molecular and Cellular Biology

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To adapt to environmental high osmolarity, the budding yeast Saccharomyces cerevisiae activates the Hog1 mitogen-activated protein kinase, which regulates diverse osmoadaptive responses. Hog1 is activated through the high-osmolarity glycerol (HOG) pathway, which consists of independent upstream signaling routes termed the SLN1 branch and the SHO1 branch. Here, we report that the extracellular cysteine-rich (CR) domain of the transmembrane-anchor protein Opy2 binds to the Hkr1-Msb2 homology (HMH) domain of the putative osmosensor Msb2 and that formation of the Opy2-Msb2 complex is essential for osmotic activation of Hog1 through the MSB2 subbranch of the SHO1 branch. By analyzing the phenotypes of mutants with Opy2 cysteine-to-alanine mutations, we deduced that the CR domain forms four intramolecular disulfide bonds. To probe for the potential induction of conformational changes in the Opy2-Msb2 complex by osmostress, we constructed mutants with a site-specific Cys-to-Ala mutation of the Opy2 CR domain and mutants with a Cys substitution of the Msb2 HMH domain. Each of these mutants had a reduced cysteine. These mutants were then combinatorially cross-linked using chemical cross-linkers of different lengths. Cross-linking between Opy2 Cys48 and Msb2 Cys1023 was sensitive to osmotic changes, suggesting that osmostress induced a conformational change. We therefore propose that the Opy2-Msb2 complex might serve as an osmosensor. Survival of living organisms depends on their ability to adapt to adverse environmental conditions. A well-known example is the response of the budding yeast Saccharomyces cerevisiae to high external osmolarity. When exposed to high osmolarity, yeast cells initiate a coordinated adaptive response that includes the synthesis and accumulation of the compatible osmolyte glycerol, changes in the global pattern of gene expression and protein synthesis, and a temporary arrest of cell cycle progression (1-3). These responses are controlled by the Hog1 mitogen-activated protein kinase (MAPK), which is activated via the high-osmolarity glycerol (HOG) signal pathway. The HOG pathway employs multiple and redundant routes between the input (external high osmolarity) and the output (Hog1-dependent responses). Specifically, the HOG pathway consists of two independent upstream signaling routes termed the SLN1 branch and the SHO1 branch (Fig. 1A). The osmosensor for the SLN1 branch is the sensor histidine kinase Sln1, which transmits the signal through a two-component phosphorelay mechanism to the redundant MAPK kinase kinases (MAPKKKs) Ssk2 and Ssk22 (4, 5). Ssk2/Ssk22 activates the Pbs2 MAPK kinase (MAPKK), which eventually activates the Hog1 MAPK (5-8).When the SLN1 branch is inactivated by the ssk2⌬ ssk22⌬ double mutation (here abbreviated ssk2/22⌬), yeast can still adapt to high osmolarity using the SHO1 branch. The major osmosensor for the SHO1 branch is the four-transmembrane (TM) protein Sho1 (5, 9). In the SHO1 branch, osmostress activates the Ste11 MAPKKK, which then sequentially activates Pbs2 an...

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The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

Cited by 52 publications

References 146 publications

Cdc42p-Interacting Protein Bem4p Regulates the Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

Cdc42p-Interacting Protein Bem4p Regulates the Filamentous-Growth Mitogen-Activated Protein Kinase Pathway

Global Regulation of a Differentiation MAPK Pathway in Yeast

Binding of the Extracellular Eight-Cysteine Motif of Opy2 to the Putative Osmosensor Msb2 Is Essential for Activation of the Yeast High-Osmolarity Glycerol Pathway

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