Regulation of intrinsic polarity establishment by a differentiation-type MAPK pathway in <i>S. cerevisiae</i>

Prabhakar, Aditi; Chow, Jacky; Siegel, Alan J.; Cullen, Paul J.

doi:10.1242/jcs.241513

Cited by 13 publications

(44 citation statements)

References 197 publications

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“…Time-lapse fluorescence microscopy was performed as described 132 . Cells were grown for 16 h in in S-D-URA + 0.1% MSG + 0.36 mg/ml Gent at 30 °C.…”

Section: Analysis Of a Gene Overexpression Collection For Altered Actmentioning

confidence: 99%

A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast

Jamalzadeh

Pujari

Cullen

2020

Sci Rep

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MAPK pathways regulate different responses yet can share common components. Although core regulators of MAPK pathways are well known, new pathway regulators continue to be identified. Overexpression screens can uncover new roles for genes in biological processes and are well suited to identify essential genes that cannot be evaluated by gene deletion analysis. In this study, a genome-wide screen was performed to identify genes that, when overexpressed, induce a reporter (FUS1-HIS3) that responds to ERK-type pathways (Mating and filamentous growth or fMAPK) but not p38-type pathways (HOG) in yeast. Approximately 4500 plasmids overexpressing individual yeast genes were introduced into strains containing the reporter by high-throughput transformation. Candidate genes were identified by measuring growth as a readout of reporter activity. Fourteen genes were identified and validated by re-testing: two were metabolic controls (HIS3, ATR1), five had established roles in regulating ERK-type pathways (STE4, STE7, BMH1, BMH2, MIG2) and seven represent potentially new regulators of MAPK signaling (RRN6, CIN5, MRS6, KAR2, TFA1, RSC3, RGT2). MRS6 encodes a Rab escort protein and effector of the TOR pathway that plays a role in nutrient signaling. MRS6 overexpression stimulated invasive growth and phosphorylation of the ERK-type fMAPK, Kss1. Overexpression of MRS6 reduced the osmotolerance of cells and phosphorylation of the p38/HOG MAPK, Hog1. Mrs6 interacted with the PAK kinase Ste20 and MAPKK Ste7 by two-hybrid analysis. Based on these results, Mrs6 may selectively propagate an ERK-dependent signal. Identifying new regulators of MAPK pathways may provide new insights into signal integration among core cellular processes and the execution of pathway-specific responses.

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“…Time-lapse fluorescence microscopy was performed as described 132 . Cells were grown for 16 h in in S-D-URA + 0.1% MSG + 0.36 mg/ml Gent at 30 °C.…”

Section: Analysis Of a Gene Overexpression Collection For Altered Actmentioning

confidence: 99%

A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast

Jamalzadeh

Pujari

Cullen

2020

Sci Rep

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“…Cells containing another hyperactive version of Msb2p, Msb2p Δ100-818 , Msb2p**, hyperactivated the fMAPK pathway through positive feedback, because the transcription factor Ste12p was required [Fig. 4E, P~Kss1, (CULLEN et al 2004;VADAIE et al 2008;PRABHAKAR et al 2020 We also examined the activity of the HOG pathway under this condition. In addition to osmotic stress, the HOG pathway can also be induced by the non-preferred carbon source, galactose (ADHIKARI AND CULLEN 2014).…”

Section: Positive Feedback Of the Fmapk Pathway Induces The Hog Pathwaymentioning

confidence: 99%

“…(VANDERMEULEN AND CULLEN 2020). Cell synchronization experiments were performed as previously described (BREEDEN 1997;PRABHAKAR et al 2020). Overnight cultures were resuspended in fresh media and grown to an optical density (O.D.)…”

Section: Cell Synchronization and Cell-cycle Experimentsmentioning

confidence: 99%

“…However, relatively little is known about how MAPK pathways are themselves regulated throughout the cell cycle. We previously found that the activity of the fMAPK pathway fluctuates throughout the cell cycle (P rabhakar et al 2020), which provided an opportunity to explore this question in depth. We show here that the fMAPK and the HOG pathways show different patterns of cell-cycle regulation.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, cell-cycle regulation of the fMAPK pathway may occur through multiple mechanisms.Coupling the activity of the fMAPK pathway to the cell cycle may occur for the pathway to regulate intrinsic polarity, which occurs in G1, under some conditions(PRABHAKAR et al 2020). Coupling the activity of the fMAPK pathway to the cell cycle may also impact its ability to regulate filamentous growth.…”

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confidence: 99%

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Spatiotemporal Control of Pathway Sensors and Cross-Pathway Feedback Regulate a Cell Differentiation MAPK Pathway in Yeast

Prabhakar

González²,

Dionne³

et al. 2020

Preprint

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Mitogen-Activated Protein Kinase (MAPK) pathways control cell differentiation and the response to stress. MAPK pathways can share components with other pathways yet induce specific responses through mechanisms that remain unclear. In Saccharomyces cerevisiae, the MAPK pathway that controls filamentous growth (fMAPK) shares components with the MAPK pathway that regulates the response to osmotic stress (HOG). By exploring temporal regulation of MAPK signaling, we show here that the two pathways exhibited different patterns of activity throughout the cell cycle. The different patterns resulted from different expression profiles of genes encoding the mucin sensors (MSB2 for fMAPK and HKR1 for HOG). We also show that positive feedback through the fMAPK pathway stimulated the HOG pathway, presumably to modulate fMAPK pathway activity. By exploring spatial regulation of MAPK signaling, we found that the shared tetraspan protein, Sho1p, which has a dynamic localization pattern, induced the fMAPK pathway at the mother-bud neck. A Sho1p-interacting protein, Hof1p, which also localizes to the mother-bud neck and regulates cytokinesis, also regulated the fMAPK pathway. Therefore, spatial and temporal regulation of pathway sensors, and cross-pathway feedback, regulate a MAPK pathway that controls a cell differentiation response in yeast.

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Self-Organization in the Cell

Maly

2021

Quantitative Elements of General Biology

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Regulation of intrinsic polarity establishment by a differentiation-type MAPK pathway in S. cerevisiae

Cited by 13 publications

References 197 publications

A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast

A Rab escort protein regulates the MAPK pathway that controls filamentous growth in yeast

Spatiotemporal Control of Pathway Sensors and Cross-Pathway Feedback Regulate a Cell Differentiation MAPK Pathway in Yeast

Self-Organization in the Cell

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