Choosing the right lifestyle: adhesion and development in<i>Saccharomyces cerevisiae</i>

Brückner, Stefan; Mösch, Hans‐Ulrich

doi:10.1111/j.1574-6976.2011.00275.x

Cited by 156 publications

(221 citation statements)

References 452 publications

(721 reference statements)

Supporting

Mentioning

217

Contrasting

Unclassified

Order By: Relevance

“…However, the finding that most BYxYJM segregants that show FLO8-independent invasion require FLO11 suggests that FLO11 expression is an important component of most of the regulatory architectures. This is of note because FLO11 has one of the largest promoters in the yeast genome and is thought to be influenced by at least 8 pathways and 15 transcription factors, as well as linked noncoding RNAs and chromatin remodeling complexes (Bruckner and Mosch 2012). The potential of FLO11 to be regulated by a number of different pathways may facilitate some of the variability in wiring that we have described.…”

Section: Resultsmentioning

confidence: 92%

“…In addition to FLO11, S. cerevisiae possesses other cell surface proteins that can contribute to adhesion-related traits [as described in Guo et al (2000) and Halme et al (2004) and elsewhere]. In some cases, these cell surface proteins are regulated by multiple signaling cascades (Bruckner and Mosch 2012), potentially providing an opportunity for genetic variants in different pathways to have similar effects on invasion.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Regulatory Rewiring in a Cross Causes Extensive Genetic Heterogeneity

et al. 2015

View full text Add to dashboard Cite

Genetic heterogeneity occurs when individuals express similar phenotypes as a result of different underlying mechanisms. Although such heterogeneity is known to be a potential source of unexplained heritability in genetic mapping studies, its prevalence and molecular basis are not fully understood. Here we show that substantial genetic heterogeneity underlies a model phenotype-the ability to grow invasively-in a cross of two Saccharomyces cerevisiae strains. The heterogeneous basis of this trait across genotypes and environments makes it difficult to detect causal loci with standard genetic mapping techniques. However, using selective genotyping in the original cross, as well as in targeted backcrosses, we detected four loci that contribute to differences in the ability to grow invasively. Identification of causal genes at these loci suggests that they act by changing the underlying regulatory architecture of invasion. We verified this point by deleting many of the known transcriptional activators of invasion, as well as the gene encoding the cell surface protein Flo11 from five relevant segregants and showing that these individuals differ in the genes they require for invasion. Our work illustrates the extensive genetic heterogeneity that can underlie a trait and suggests that regulatory rewiring is a basic mechanism that gives rise to this heterogeneity.KEYWORDS complex traits; genetic mapping; invasive growth; regulatory networks; yeast G ENETIC studies in humans and model organisms have reported unexplained heritability for many traits (Manolio et al. 2009). A possible contributor to this "missing" heritability is genetic heterogeneity-individuals exhibiting similar phenotypes owing to different genetic and molecular mechanisms (Risch 2000;McClellan and King 2010;Wray and Maier 2014). Genetic heterogeneity can reduce the statistical power of mapping studies (Manchia et al. 2013;Wray and Maier 2014) and may involve multiple variants segregating in the same gene (allelic heterogeneity) or different genes (nonallelic heterogeneity) (Risch 2000). Work to date has shown that allelic heterogeneity is widespread (e.g., McClellan and King 2010;Ehrenreich et al. 2012;Long et al. 2014) and often involves two or more null or partial loss-of-function variants segregating in a single phenotypically important gene (e.g., Nogee et al. 2000;Sutcliffe et al. 2005;Will et al. 2010). However, the prominence and underlying mechanisms of nonallelic heterogeneity are less understood.In this paper we describe an example of nonallelic heterogeneity using heritable variation in the ability of Saccharomyces cerevisiae strains to undergo haploid invasive growth as our model. Invasive growth is a phenotype that is triggered by low carbon or nitrogen availability and is thought to be an adaptive response that allows yeast cells to adhere to and penetrate surfaces (Cullen and Sprague 2000). Invasion typically requires expression of FLO11, which encodes a cell surface glycoprotein that facilitates cell-cell and cell-surface adhes...

show abstract

Section: Resultsmentioning

confidence: 92%

mentioning

confidence: 99%

Regulatory Rewiring in a Cross Causes Extensive Genetic Heterogeneity

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Multicellullar phenotypes, like flocculation and florulation, promote the removal of yeast following alcohol fermentation, and these traits have been selected by brewers (Briggs et al 2004;Verstrepen and Klis 2006;Bruckner and Mosch 2011). The ability of a strain to make contact and adhere to another yeast apparently evolved as a social response to stress, as flocs are protected from toxins like alcohol and antimicrobial compounds (Smukalla et al 2008).…”

Section: Risk Factors For [Pin+] Infectionmentioning

confidence: 99%

“…Additionally, flocculation, characterized by increased cell-cell adhesion resulting in aggregates of vegetative cells, is often observed when sugars are depleted from the media (Guo et al 2000). Enhanced cellular aggregation provides protection in harsh environments (Bruckner and Mosch 2011), and flocculent yeast strains are often utilized in beer fermentation and other industrialized settings (Verstrepen and Klis 2006).…”

mentioning

confidence: 99%

Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

2014

View full text Add to dashboard Cite

Prions (infectious proteins) cause fatal neurodegenerative diseases in mammals. In the yeast Saccharomyces cerevisiae, many toxic and lethal variants of the [PSI+] and [URE3] prions have been identified in laboratory strains, although some commonly studied variants do not seem to impair cell growth. Phylogenetic analysis has revealed four major clades of S. cerevisiae that share histories of two prion proteins and largely correspond to different ecological niches of yeast. The [PIN+] prion was most prevalent in commercialized niches, infrequent among wine/vineyard strains, and not observed in ancestral isolates. As previously reported, the [PSI+] and [URE3] prions are not found in any of these strains. Patterns of heterozygosity revealed genetic mosaicism and indicated extensive outcrossing among divergent strains in commercialized environments. In contrast, ancestral isolates were all homozygous and wine/vineyard strains were closely related to each other and largely homozygous. Cellular growth patterns were highly variable within and among clades, although ancestral isolates were the most efficient sporulators and domesticated strains showed greater tendencies for flocculation.[PIN+]-infected strains had a significantly higher likelihood of polyploidy, showed a higher propensity for flocculation compared to uninfected strains, and had higher sporulation efficiencies compared to domesticated, uninfected strains. Extensive phenotypic variability among strains from different environments suggests that S. cerevisiae is a niche generalist and that most wild strains are able to switch from asexual to sexual and from unicellular to multicellular growth in response to environmental conditions. Our data suggest that outbreeding and multicellular growth patterns adapted for domesticated environments are ecological risk factors for the [PIN+] prion in wild yeast. P RIONS cause a variety of transmissible spongiform encephalopathies (TSEs) in mammals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and CreutzfeldtJakob disease (CJD) in humans. With all TSEs, endogenous prion protein (PrP) misfolds into an altered, usually proteaseresistant, isoform, termed "PrP res " (" res" for protease resistant). Several prions have been described in fungi (Wickner 1994), with many prion variants of the [PSI+] and [URE3] prions showing toxic or even lethal effects in Saccharomyces cerevisiae (McGlinchey et al. 2011). The [PSI+] prion of S. cerevisiae is formed from the cytosolic protein Sup35p. There are three distinct regions of Sup35p: a glutamine/ asparagine-rich N-terminal domain (amino acids 1-123) that is necessary and sufficient for prion formation (TerAvanesyan et al. 1994) and that facilitates deadenylation and decay of messenger RNA (Hosoda et al. 2003); a middle M domain (amino acids 124-253) of unknown function; and an essential C-terminal domain that functions during translation termination (reviewed by Wickner et al. 2004 (Derkatch et ...

show abstract

“…Yak1-dependent functions of Whi3 further include control of stress responses via the transcription factors Msn2 and Msn4 (Lee et al 2008) and acidic stress resistance mediated by the transcriptional regulator Haa1 (Fernandes et al 2005;Malcher et al 2011). However, Whi3 also seems to control filamentation and biofilm formation by yet unknown Yak1-independent mechanisms (Malcher et al 2011), which might include other components of the complex signaling network that controls FLO11 (Brückner and Mösch 2012).…”

mentioning

confidence: 99%

The RNA-Binding Protein Whi3 Is a Key Regulator of Developmental Signaling and Ploidy inSaccharomyces cerevisiae

Schladebeck

Mösch

2013

Genetics

Self Cite

View full text Add to dashboard Cite

In Saccharomyces cerevisiae, the RNA-binding protein Whi3 controls cell cycle progression, biofilm formation, and stress response by post-transcriptional regulation of the Cdc28-Cln3 cyclin-dependent protein kinase and the dual-specificity protein kinase Yak1. Previous work has indicated that Whi3 might govern these processes by additional, yet unknown mechanisms. In this study, we have identified additional effectors of Whi3 that include the G 1 cyclins Cln1/Cln2 and two known regulators of biofilm formation, the catalytic PKA subunit Tpk1 and the transcriptional activator Tec1. We also provide evidence that Whi3 regulates production of these factors by post-transcriptional control and might exert this function by affecting translational elongation. Unexpectedly, we also discovered that Whi3 is a key regulator of cellular ploidy, because haploid whi3Δ mutant strains exhibit a significant increase-in-ploidy phenotype that depends on environmental conditions. Our data further suggest that Whi3 might control stability of ploidy by affecting the expression of many key genes involved in sister chromatid cohesion and of NIP100 that encodes a component of the yeast dynactin complex for chromosome distribution. Finally, we show that absence of Whi3 induces a transcriptional stress response in haploid cells that is relieved by whole-genome duplication. In summary, our study suggests that the RNA-binding protein Whi3 acts as a central regulator of cell division and development by post-transcriptional control of key genes involved in chromosome distribution and cell signaling. E UKARYOTIC organisms have evolved highly complex signaling networks to control cell division and development. The functionality of signal transduction pathways crucially depends on the timely availability of individual components at sufficient levels to ensure adequate signaling capacity. A number of studies in different eukaryotes have shown that the production of individual signaling proteins is under the control not only of transcriptional regulators, but also of RNA-binding proteins (Lasko 2003;Sugiura et al. 2003;Prinz et al. 2007;Stewart et al. 2007;Malcher et al. 2011). This suggests that RNA-binding proteins could regulate the performance of whole signaling networks, but a precise view of key interconnections is often lacking.In the budding yeast Saccharomyces cerevisiae, the Pumilio family (PUF) protein Mpt5/Puf5 is a good example of an RNA-binding protein that controls cellular development by targeting signaling components. Mpt5 has been found to negatively affect the performance of at least two different mitogen-activated protein kinase (MAPK) signaling pathways that regulate adhesion/biofilm formation and cell wall integrity (Prinz et al. 2007;Stewart et al. 2007). In general, PUF proteins are known to bind to the 39-UTR of target mRNAs and reduce their stability or translatability (Quenault et al. 2011). This is also true for S. cerevisiae Mpt5, which represses the protein levels of key components of the MAPK cascade that regu...

show abstract

Choosing the right lifestyle: adhesion and development inSaccharomyces cerevisiae

Cited by 156 publications

References 452 publications

Regulatory Rewiring in a Cross Causes Extensive Genetic Heterogeneity

Regulatory Rewiring in a Cross Causes Extensive Genetic Heterogeneity

Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

The RNA-Binding Protein Whi3 Is a Key Regulator of Developmental Signaling and Ploidy inSaccharomyces cerevisiae

Contact Info

Product

Resources

About