Cell wall synthesis and central carbohydrate metabolism are interconnected by the SNF1/Mig1 pathway in Kluyveromyces lactis

Rippert, Dorthe; Backhaus, Katja; Rodicio, Rosaura; Heinisch, Jürgen J.

doi:10.1016/j.ejcb.2016.12.004

Cited by 10 publications

(4 citation statements)

References 66 publications

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“…Additional work in S . cerevisiae and other yeasts of the Saccharomycotina has shown that the kinase Snf1p plays an important role in Mig1p activity via phosphorylation (Matsuzawa et al 2012 ; Rippert et al 2017 ; Treitel et al 1998 ).…”

Section: Transcriptional Regulationmentioning

confidence: 99%

Protein hyperproduction in fungi by design

Baker

2018

Appl Microbiol Biotechnol

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The secretion of enzymes used by fungi to digest their environment has been exploited by humans for centuries for food and beverage production. More than a century after the first biotechnology patent, we know that the enzyme cocktails secreted by these amazing organisms have tremendous use across a number of industrial processes. Secreting the maximum titer of enzymes is critical to the economic feasibility of these processes. Traditional mutagenesis and screening approaches have generated the vast majority of strains used by industry for the production of enzymes. Until the emergence of economical next generation DNA sequencing platforms, the majority of the genes mutated in these screens remained uncharacterized at the sequence level. In addition, mutagenesis comes with a cost to an organism’s fitness, making tractable rational strain design approaches an attractive alternative. As an alternative to traditional mutagenesis and screening, controlled manipulation of multiple genes involved in processes that impact the ability of a fungus to sense its environment, regulate transcription of enzyme-encoding genes, and efficiently secrete these proteins will allow for rational design of improved fungal protein production strains.

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Section: Transcriptional Regulationmentioning

confidence: 99%

Protein hyperproduction in fungi by design

Baker

2018

Appl Microbiol Biotechnol

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“…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%

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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“…TORC2 phosphorylates and stimulates the downstream protein kinase Ypk1/ Ypk2 to regulate membrane lipids and proteins (26,27). In addition, the Snf1 pathway is involved in regulation of cell membrane biosynthesis, given that deletion of the subunits of the SNF1 complex resulted in hypersensitivity to cell membrane stress (28,29). Moreover, the Snf1 pathway has been proposed to have an additional function of coordinating membrane transport proteins, which is an important strategy for achieving the fast rearrangement of the plasma membrane to resist stress, apart from coordinating transcriptional gene expression (30,31).…”

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confidence: 99%

Cg Hog1-Mediated Cg Rds2 Phosphorylation Alters Glycerophospholipid Composition To Coordinate Osmotic Stress in Candida glabrata

Zhang

Zhu

et al. 2019

Appl Environ Microbiol

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Under stress conditions, Hog1 is required for cell survival through transiently phosphorylating downstream targets and reprogramming gene expression. Here, we report that Candida glabrata Hog1 (CgHog1) interacts with and phosphorylates CgRds2, a zinc cluster transcription factor, in response to osmotic stress. Additionally, we found that deletion of CgRDS2 led to decreases in cell growth and cell survival by 23.4% and 39.6%, respectively, at 1.5 M NaCl, compared with levels of the wild-type strain. This is attributed to significant downregulation of the expression levels of glycerophospholipid metabolism genes. As a result, the content of total glycerophospholipid decreased by 30.3%. Membrane integrity also decreased 47.6% in the Cgrds2Δ strain at 1.5 M NaCl. In contrast, overexpression of CgRDS2 increased the cell growth and cell survival by 10.2% and 6.3%, respectively, owing to a significant increase in the total glycerophospholipid content and increased membrane integrity by 27.2% and 12.1%, respectively, at 1.5 M NaCl, compared with levels for the wild-type strain. However, a strain in which the CgRDS2 gene encodes the replacement of Ser64 and Thr97 residues with alanines (Cgrds22A), harboring a CgRds2 protein that was not phosphorylated by CgHog1, failed to promote glycerophospholipid metabolism and membrane integrity at 1.5 M NaCl. Thus, the above results demonstrate that CgHog1-mediated CgRds2 phosphorylation enhanced glycerophospholipid composition and membrane integrity to resist osmotic stress in C. glabrata. IMPORTANCE This study explored the role of CgHog1-mediated CgRds2 phosphorylation in response to osmotic stress in Candida glabrata. CgHog1 interacts with and phosphorylates CgRds2, a zinc cluster transcription factor, under osmotic stress. Phosphorylated CgRds2 plays an important role in increasing glycerophospholipid composition and membrane integrity, thereby enhancing cell growth and survival.

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Cell wall synthesis and central carbohydrate metabolism are interconnected by the SNF1/Mig1 pathway in Kluyveromyces lactis

Cited by 10 publications

References 66 publications

Protein hyperproduction in fungi by design

Protein hyperproduction in fungi by design

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

Cg Hog1-Mediated Cg Rds2 Phosphorylation Alters Glycerophospholipid Composition To Coordinate Osmotic Stress in Candida glabrata

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