Mutations in SNF1 complex genes affect yeast cell wall strength

Backhaus, Katja; Rippert, Dorthe; Heilmann, Clemens J.; Sorgo, Alice G.; Koster, Chris G. de; Klis, Frans M.; Rodicio, Rosaura; Heinisch, Jürgen J.

doi:10.1016/j.ejcb.2014.01.001

Cited by 34 publications

(28 citation statements)

References 75 publications

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“…In contrast, the ras1 deletion displayed only a moderate increase in resistance towards the cell wall stress agents. Note that mutants in the independent SNF1 signaling pathway were previously shown to be hyper-sensitive to the same agents and thus not included in these assays [13]. Taken together, these data further support a crosstalk of CWI and specific branches of the glucose signaling pathways, which could be mediated by Rho5.…”

Section: Resultssupporting

confidence: 59%

“…Of those, the SNF1 complex participates in the regulation of cell wall composition, suggested by the sensitivity of null mutants towards cell wall stress agents both in S. cerevisiae and in the milk yeast Kluyveromyces lactis [13,14]. In addition, Ras2/cAMP-signaling was also found to affect CWI signaling through genetic interactions and in transcriptome studies [15,16], as well as influencing the dynamics of the actin cytoskeleton [17,18], mitochondrial morphogenesis [19], pH homeostasis [20], and apoptosis [21].…”

Section: Introductionmentioning

confidence: 99%

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The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

Schmitz

Jendretzki

Sterk

et al. 2018

IJMS

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Rho5 is a small GTPase of Saccharomyces cerevisiae and a homolog of mammalian Rac1. The latter regulates glucose metabolism and actin cytoskeleton dynamics, and its misregulation causes cancer and a variety of other diseases. In yeast, Rho5 has been implicated in different signal transduction pathways, governing cell wall integrity and the responses to high medium osmolarity and oxidative stress. It has also been proposed to affect mitophagy and apoptosis. Here, we demonstrate that Rho5 rapidly relocates from the plasma membrane to mitochondria upon glucose starvation, mediated by its dimeric GDP/GTP exchange factor (GEF) Dck1/Lmo1. A function in response to glucose availability is also suggested by synthetic genetic phenotypes of a rho5 deletion with gpr1, gpa2, and sch9 null mutants. On the other hand, the role of mammalian Rac1 in regulating the action cytoskeleton does not seem to be strongly conserved in S. cerevisiae Rho5. We propose that Rho5 serves as a central hub in integrating various stress conditions, including a crosstalk with the cAMP/PKA (cyclic AMP activating protein kinase A) and Sch9 branches of glucose signaling pathways.

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Section: Resultssupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

Schmitz

Jendretzki

Sterk

et al. 2018

IJMS

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show abstract

“…1), but we suggest that this could be an 527 adaptation phenomenon induced by the metabolic changes, as observed 528 also in mammalian cells [42]. Notably, it was recently observed that 529 mutants of the Snf1 pathway present a thinner cell wall and a higher 530 susceptibility to agents targeting this structure [43]. This effect is nicely 531 reverted by deletion of PFK1, which restores the glucose-6-phosphate 532 pool, which is reduced in snf1Δ cells.…”

mentioning

confidence: 82%

Enhanced amino acid utilization sustains growth of cells lacking Snf1/AMPK

Nicastro

Tripodi

Guzzi

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The metabolism of proliferating cells shows common features even in evolutionary distant organisms such as mammals and yeasts, for example the requirement for anabolic processes under tight control of signaling pathways. Analysis of the rewiring of metabolism, which occurs following the dysregulation of signaling pathways, provides new knowledge about the mechanisms underlying cell proliferation. The key energy regulator in yeast Snf1 and its mammalian ortholog AMPK have earlier been shown to have similar functions at glucose limited conditions and here we show that they also have analogies when grown with glucose excess. We show that loss of Snf1 in cells growing in 2% glucose induces an extensive transcriptional reprogramming, enhances glycolytic activity, fatty acid accumulation and reliance on amino acid utilization for growth. Strikingly, we demonstrate that Snf1/AMPK-deficient cells remodel their metabolism fueling mitochondria and show glucose and amino acids addiction, a typical hallmark of cancer cells.

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“…As a last example of using established yeast mutants and chimeric yeast/human enzymes the yeast SNF1 complex was discovered years before its human homolog AMPK, both being involved in energy signaling (see [103], and references therein). As shown in Fig.…”

Section: Genetic Screens In Yeast -The Past the Present And The Futurementioning

confidence: 99%

“…2, besides being a target of the protein phosphatase PP2A in humans, it mediates the phosphorylation state of tau both directly and indirectly through regulation of GSK3ß kinase activity. Deletion mutants in all three subunits of the complex are readily available in different yeast strains and where shown to affect not only carbohydrate metabolism but also a variety of other signal transduction mechanisms [103]. Importantly, mammalian orthologs of the catalytic α-subunit did not complement the yeast snf1 defects, but coexpression of all three genes encoding the complex did [84].…”

Section: Genetic Screens In Yeast -The Past the Present And The Futurementioning

confidence: 99%

Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells

Heinisch¹,

Brandt²

2016

MIC

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In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. However, it has become evident that substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. This is exemplified by the neuronal tau proteins, which are critically involved in a class of neurodegenerative diseases collectively called tauopathies and which includes Alzheimer's disease (AD) as its most common representative. In the course of the disease, tau changes its phosphorylation state and becomes hyperphosphorylated, gets truncated by proteolytic cleavage, is subject to O-glycosylation, sumoylation, ubiquitinylation, acetylation and some other modifications. This poses the important question, which of these posttranslational modifications are naturally occurring in the yeast model or can be reconstituted by heterologous gene expression. Here, we present an overview on common modifications as they occur in tau during AD, summarize their potential relevance with respect to disease mechanisms and refer to the native yeast enzyme orthologs capable to perform these modifications. We will also discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells, which could enhance the value of Saccharomyces cerevisiae and Kluyveromyces lactis as disease models.

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Mutations in SNF1 complex genes affect yeast cell wall strength

Cited by 34 publications

References 75 publications

The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

Enhanced amino acid utilization sustains growth of cells lacking Snf1/AMPK

Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells

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