Rlm1 mediates positive autoregulatory transcriptional feedback that is essential for Slt2-dependent gene expression

García, Raúl; Sanz, Ana B.; Rodrı́guez-Peña, José Manuel; Nombela, César; Arroyo, Javier

doi:10.1242/jcs.180190

Cited by 41 publications

(39 citation statements)

References 76 publications

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“…The second approach that we employed was the deletion of MSG5 . In the absence of stress, phosphatases like Msg5, Ptp3 and Sdp1 maintain Slt2 in either inactive state or a low activity state (García et al , ; Liu and Levin, ). We observed an increase in Slt2 phosphorylation in msg5 ∆ cells in comparison to wild‐type cells indicating that the CWI pathway is activated in the absence of Msg5 phosphatase (Fig.…”

Section: Resultsmentioning

confidence: 99%

Flocculation of Saccharomyces cerevisiae is dependent on activation of Slt2 and Rlm1 regulated by the cell wall integrity pathway

Sariki

Kumawat

Singh

et al. 2019

Molecular Microbiology

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Summary Flocculation is an essential characteristic of yeast cells required for survival under adverse conditions. The multicellular structure (flocs) of yeast provides a suitable microenvironment to enhance the chances of survival during stress conditions. Although the signaling events triggering flocculation have been studied earlier, molecular mechanisms remain elusive. In the present study, we used flocculating sen1 mutants to identify the mechanism of flocculation. Based on the abnormal cell surface morphology and constitutive phosphorylation of Slt2p in flocculating sen1 mutant cells, we hypothesized if flocculation was regulated by the cell wall integrity (CWI) pathway. Up‐regulation of FLO genes in wild‐type cells was observed upon the activation of CWI pathway either by chemical treatment or by deleting Slt2 phosphatase (Msg5). Our study with Slt2 mutants reveals that the active state of Slt2 is indispensable for flocculation. Deletion of either SLT2 or RLM1 leads to reduced flocculation. Furthermore, we observed overlapping binding sites for Rlm1 and Tup1 at the promoters of almost all the FLO genes. Finally, we show higher Rlm1 and lower Tup1 occupancy at the promoters of FLO1 and FLO5 in flocculating cells. Altogether we demonstrate that CWI MAPK (Slt2) pathway uses a non‐catalytic mechanism to activate the transcription of FLO genes.

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Section: Resultsmentioning

confidence: 99%

Flocculation of Saccharomyces cerevisiae is dependent on activation of Slt2 and Rlm1 regulated by the cell wall integrity pathway

Sariki

Kumawat

Singh

et al. 2019

Molecular Microbiology

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“…These results are indicative of positive transcriptional feedback loops of Ace2 on most upstream components of the Cek1 pathway. In a similar manner, the cell wall integrity pathway of the apathogenic yeast S. cerevisiae appears regulated, since a positive feedback by the Rlm1 transcription factor on its encoding gene and on that for the upstream Slt2 MAPK was reported recently (García et al ., ). Positive feedback regulation is expected to strongly boost the activity of MAPK pathways by increasing levels of the respective pathway components.…”

Section: Discussionmentioning

confidence: 99%

Candida albicans responds to glycostructure damage by Ace2‐mediated feedback regulation of Cek1 signaling

Wijlick

Swidergall

Brandt

et al. 2016

Molecular Microbiology

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Candida albicans uses the Cek1 MAPK pathway to restore cells from damage of its cell wall glycostructures. Defective protein N- or O-glycosylation activates Cek1 and the transcription factor Ace2 as its downstream target, to upregulate genes encoding protein O-mannosyltransferases (Pmt proteins). In unstressed cells, Cek1-Ace2 activity blocks expression of PMT1, which is de-repressed by tunicamycin. Genomic binding targets of Ace2 included ZCF21, which was upregulated by Ace2 and found to repress PMT1 transcription in unstressed cells. Surprisingly, genes encoding components of the Cek1 pathway including MSB2, CST20, HST7, CEK1 and ACE2 were also identified as Ace2 targets indicating Ace2-mediated transcriptional amplification of pathway genes under N-glycosylation stress. In this condition, physical interaction of the Ace2 protein with the upstream MAPKKK Cst20 was detected. Cst20-GFP showed stress-induced import from the cytoplasm into the nucleus and phosphorylation of Ace2. Interestingly, forced nuclear localization of Cst20 inhibited Cek1-Ace2 signaling, while forced cytoplasmic localization of Cst20 retained full signaling activity, suggesting that nuclear Cst20 downregulates the Cek1 pathway. Collectively, the results indicate that Ace2 is a versatile multifunctional transcriptional regulator, which activates glycostress responses of C. albicans by both positive forward and negative feedback regulation of Cek1 signaling.

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“…To test this assumption, the activation state of the CWI pathway was assessed by determining the dual phosphorylation of the downstream MAP kinase Slt2 (Martín et al, 2000). This relation was not significantly altered when transketolase was employed as an internal standard protein for normalization of the phosphorylated Slt2 signal, indicating that the autoregulatory circuit in Slt2 activation reported by Garcia et al (2016) does not have a major influence. After stress induction a wsc1 deletion strain displayed a reduction in the phosphorylation level of Slt2 to 60% of that of a wild-type strain when normalized to the non-phosphorylated Slt2 signal (Fig.…”

Section: Wsc1 Sensosome Formation and Its Signalling Function Depend mentioning

confidence: 99%

Yeast cell wall integrity sensors form specific plasma membrane microdomains important for signalling

Kock

Arlt

Ungermann

et al. 2016

Cellular Microbiology

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The cell wall integrity (CWI) pathway of the yeast Saccharomyces cerevisiae relies on the detection of cell surface stress by five sensors (Wsc1, Wsc2, Wsc3, Mid2, Mtl1). Each sensor contains a single transmembrane domain and a highly mannosylated extracellular region, and probably detects mechanical stress in the cell wall or the plasma membrane. We here studied the distribution of the five sensors at the cell surface by using fluorescently tagged variants in conjunction with marker proteins for established membrane compartments. We find that each of the sensors occupies a specific microdomain at the plasma membrane. The novel punctate 'membrane compartment occupied by Wsc1' (MCW) shows moderate overlap with other Wsc-type sensors, but not with those of the Mid-type sensors or other established plasma membrane domains. We further observed that sensor density and formation of the MCW compartment depends on the cysteine-rich head group near the N-terminus of Wsc1. Yet, signalling capacity depends more on the sensor density in the plasma membrane than on clustering within its microcompartment. We propose that the MCW microcompartment provides a quality control mechanism for retaining functional sensors at the plasma membrane to prevent them from endocytosis.

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Rlm1 mediates positive autoregulatory transcriptional feedback that is essential for Slt2-dependent gene expression

Cited by 41 publications

References 76 publications

Flocculation of Saccharomyces cerevisiae is dependent on activation of Slt2 and Rlm1 regulated by the cell wall integrity pathway

Flocculation of Saccharomyces cerevisiae is dependent on activation of Slt2 and Rlm1 regulated by the cell wall integrity pathway

Candida albicans responds to glycostructure damage by Ace2‐mediated feedback regulation of Cek1 signaling

Yeast cell wall integrity sensors form specific plasma membrane microdomains important for signalling

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