Pleiotropic signaling pathways orchestrate yeast development

Granek, Joshua A.; Kayıkçı, Ömür; Magwene, Paul M.

doi:10.1016/j.mib.2011.09.004

Cited by 37 publications

(34 citation statements)

References 71 publications

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“…Filamentous growth is a differentiation response that can be quantitatively studied by clear-cut biological and biochemical assays (20,91,92). To define the role of Bem4p in regulating filamentous growth, the BEM4 gene was disrupted in haploid (MATa) and diploid (MATa/MAT␣) strains of the filamentous (⌺1278b) background.…”

Section: Bem4pmentioning

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: Bem4pmentioning

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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“…This property gives rise to the idea that “everything regulates everything else” and fuels the question of what mechanisms cells have evolved to selectively activate particular signaling molecules and pathways (Kiel and Serrano, 2012b), without inevitably having broad pleiotropic effects on the entire signaling architecture (Granek et al, 2011; Guruharsha et al, 2012; Kiel and Serrano, 2012a). …”

Section: Signaling Network Are Highly Interconnectedmentioning

confidence: 99%

Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes

Blind

2014

Advances in Biological Regulation

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An unresolved problem in biological signal transduction is how particular branches of highly interconnected signaling networks can be decoupled, allowing activation of specific circuits within complex signaling architectures. Although signaling dynamics and spatiotemporal mechanisms serve critical roles, it remains unclear if these are the only ways cells achieve specificity within networks. The transcription factor Steroidogenic Factor-1 (SF-1) is an excellent model to address this question, as it forms dynamic complexes with several chemically distinct lipid species (phosphatidylinositols, phosphatidylcholines and sphingolipids). This property is important since lipids bound to SF-1 are modified by lipid signaling enzymes (IPMK & PTEN), regulating SF-1 biological activity in gene expression. Thus, a particular SF-1/lipid complex can interface with a lipid signaling enzyme only if SF-1 has been loaded with a chemically compatible lipid substrate. This mechanism permits dynamic downstream responsiveness to constant upstream input, disentangling specific pathways from the full network. The potential of this paradigm to apply generally to nuclear lipid signaling is discussed, with particular attention given to the nuclear receptor superfamily of transcription factors and their phospholipid ligands.

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“…As one of the few observations of segregating variation acting at multiple levels of a genetic network (Gerke et al 2009), these results provide novel insights into the role of network variation on complex traits. Because the cAMP-PKA pathway is a pleiotropic regulator of many developmental switches in fungi (Granek et al 2011;McDonough and Rodriguez 2012), including many that are important for pathogenesis (Hall et al 2010;Yi et al 2011), our findings will serve as an important guide for future efforts aimed at understanding natural variation in fungal development and morphogenesis.…”

mentioning

confidence: 92%

The Genetic Architecture of Biofilm Formation in a Clinical Isolate of Saccharomyces cerevisiae

et al. 2013

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Biofilms are microbial communities that form on surfaces. They are the primary form of microbial growth in nature and can have detrimental impacts on human health. Some strains of the budding yeast Saccharomyces cerevisiae form colony biofilms, and there is substantial variation in colony architecture between biofilm-forming strains. To identify the genetic basis of biofilm variation, we developed a novel version of quantitative trait locus mapping, which leverages cryptic variation in a clinical isolate of S. cerevisiae. We mapped 13 loci linked to heterogeneity in biofilm architecture and identified the gene most closely associated with each locus. Of these candidate genes, six are members of the cyclic AMP-protein kinase A pathway, an evolutionarily conserved cell signaling network. Principal among these is CYR1, which encodes the enzyme that catalyzes production of cAMP. Through a combination of gene expression measurements, cell signaling assays, and gene overexpression, we determined the functional effects of allelic variation at CYR1. We found that increased pathway activity resulting from protein coding and expression variation of CYR1 enhances the formation of colony biofilms. Four other candidate genes encode kinases and transcription factors that are targets of this pathway. The protein products of several of these genes together regulate expression of the sixth candidate, FLO11, which encodes a cell adhesion protein. Our results indicate that epistatic interactions between alleles with both positive and negative effects on cyclic AMP-protein kinase A signaling underlie much of the architectural variation we observe in colony biofilms. They are also among the first to demonstrate genetic variation acting at multiple levels of an integrated signaling and regulatory network. Based on these results, we propose a mechanistic model that relates genetic variation to gene network function and phenotypic outcomes. BIOFILMS are complex, surface-adherent communities of microbes. They are ubiquitous in nature and in the human environment (Donlan and Costerton 2002;López et al. 2010). Not only can they be life threatening when they form in the human body (Hall-Stoodley et al. 2004), but biofilms also create problems when they form on human-made structures, ranging from merely annoying (shower curtains) to hazardous (nuclear power plants) (Flemming 2002). Because of the frequency with which we interact with biofilms, characterizing the cellular mechanisms that regulate them and understanding the genetic basis of their variation are of great interest.The ability to form biofilms is a multifactorial trait, resulting from the interactions of several lower-level properties, including cell-cell and cell-substrate adhesion; production of extracellular matrix; and spatial heterogeneity in cell morphology, growth, and division. Recent studies have demonstrated that the budding yeast Saccharomyces forms microbial communities that have these biofilm characteristics (Kuthan et al. 2003;Váchová et al. 2011). These ch...

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Pleiotropic signaling pathways orchestrate yeast development

Cited by 37 publications

References 71 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

Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes

The Genetic Architecture of Biofilm Formation in a Clinical Isolate of Saccharomyces cerevisiae

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