Two-Component Histidine Phosphotransfer Protein Ypd1 Is Not Essential for Viability in Candida albicans

Mavrianos, John; Desai, Chirayu; Chauhan, Neeraj

doi:10.1128/ec.00243-13

Cited by 32 publications

(30 citation statements)

References 44 publications

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“…There are other possible advantages for a three-component architecture, including combinatorial control of response regulators by sensor proteins through a common phosphotransfer protein or segregation of sensing and activation functions between the nucleus and cytoplasm. Intriguingly, deletion of YPD1 has recently been shown to cause constitutive activation of the HOG pathway in Candida albicans , suggesting that its buffering capacity might also be important in this organism [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Robust network structure of the Sln1-Ypd1-Ssk1 three-component phospho-relay prevents unintended activation of the HOG MAPK pathway in Saccharomyces cerevisiae

Dexter

Gunawardena

et al. 2015

BMC Syst Biol

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BackgroundThe yeast Saccharomyces cerevisiae relies on the high-osmolarity glycerol (HOG) signaling pathway to respond to increases in external osmolarity. The HOG pathway is rapidly activated under conditions of elevated osmolarity and regulates transcriptional and metabolic changes within the cell. Under normal growth conditions, however, a three-component phospho-relay consisting of the histidine kinase Sln1, the transfer protein Ypd1, and the response regulator Ssk1 represses HOG pathway activity by phosphorylation of Ssk1. This inhibition of the HOG pathway is essential for cellular fitness in normal osmolarity. Nevertheless, the extent to and mechanisms by which inhibition is robust to fluctuations in the concentrations of the phospho-relay components has received little attention.ResultsWe established that the Sln1-Ypd1-Ssk1 phospho-relay is robust—it is able to maintain inhibition of the HOG pathway even after significant changes in the levels of its three components. We then developed a biochemically realistic mathematical model of the phospho-relay, which suggested that robustness is due to buffering by a large excess pool of Ypd1. We confirmed experimentally that depletion of the Ypd1 pool results in inappropriate activation of the HOG pathway.ConclusionsWe identified buffering by an intermediate component in excess as a novel mechanism through which a phospho-relay can achieve robustness. This buffering requires multiple components and is therefore unavailable to two-component systems, suggesting one important advantage of multi-component relays.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0158-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Robust network structure of the Sln1-Ypd1-Ssk1 three-component phospho-relay prevents unintended activation of the HOG MAPK pathway in Saccharomyces cerevisiae

Dexter

Gunawardena

et al. 2015

BMC Syst Biol

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“…The observation that Skn7 is not necessary for C. albicans adaptation to cell wall/osmotic stress suggests that in C. albicans Skn7 is – at least for functions related to filamentation, oxidative stress and osmotic stress tolerance – disconnected from the Sln1/Ypd1 pathway, contrary to what has been observed in S. cerevisiae . This is supported by distinct phenotypes of the C. albicans SLN1, YPD1 and SKN7 null mutants when exposed to osmotic, cell wall or oxidative stress or induced to undergo the yeast‐to‐hypha transition (Nagahashi et al ., ; Yamada‐Okabe et al ., ; Kruppa et al ., ; Singh et al ., ; Mavrianos et al ., ). Mutations of the T484 and T496 residues in the C. albicans Skn7 receiver domain affect both oxidative stress tolerance and morphogenesis.…”

Section: Discussionmentioning

confidence: 99%

The two‐component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis‐induced ROS accumulation

Basso

Znaidi

Lagage

et al. 2017

Molecular Microbiology

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Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) in filament-inducing conditions on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.

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“…Most of the information about this class of proteins has been obtained from studies of model yeast S. cerevisiae (Fassler & West, 2013). Ypd1 is essential for viability in S. cerevisiae and C. neoformans (Fassler & West, 2013;Lee et al, 2011) but not in C. albicans (Mavrianos et al, 2014). This apparent difference could be due to mechanisms unique to C. albicans, whereby the phosphotransfer can proceed from the upstream HK to the RR while bypassing Ypd1.…”

Section: Transferases (Hpt)mentioning

confidence: 98%

Two-component phosphorelays in fungal mitochondria and beyond

Chauhan

2015

Mitochondrion

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Two-Component Histidine Phosphotransfer Protein Ypd1 Is Not Essential for Viability in Candida albicans

Cited by 32 publications

References 44 publications

Robust network structure of the Sln1-Ypd1-Ssk1 three-component phospho-relay prevents unintended activation of the HOG MAPK pathway in Saccharomyces cerevisiae

Robust network structure of the Sln1-Ypd1-Ssk1 three-component phospho-relay prevents unintended activation of the HOG MAPK pathway in Saccharomyces cerevisiae

The two‐component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis‐induced ROS accumulation

Two-component phosphorelays in fungal mitochondria and beyond

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