The Mitogen-Activated Protein Kinase Slt2 Promotes Asymmetric Cell Cycle Arrest and Reduces TORC1-Sch9 Signaling in Yeast Lacking the Protein Phosphatase Ptc1

  1. González-Rubio, Gema 1
  2. Martín, Humberto 1
  3. Molina, María 1
  1. 1 Departamento de Microbiología y Parasitología. Facultad de Farmacia. Instituto Ramón y Cajal de Investigaciones Sanitarias, Universidad Complutense de Madrid, Madrid, Spain
Journal:
Microbiology Spectrum

ISSN: 2165-0497

Year of publication: 2023

Type: Article

DOI: 10.1128/SPECTRUM.05249-22 GOOGLE SCHOLAR lock_openOpen access editor

More publications in: Microbiology Spectrum

Metrics

Cited by

  • Scopus Cited by: 1 (15-02-2024)
  • Web of Science Cited by: 0 (17-10-2023)
  • Dimensions Cited by: 1 (19-01-2024)

JCR (Journal Impact Factor)

(Indicator corresponding to the last year available on this portal, year 2022)
  • Year 2022
  • Journal Impact Factor: 3.7
  • Journal Impact Factor without self cites: 3.5
  • Article influence score: 1.439
  • Best Quartile: Q2
  • Area: MICROBIOLOGY Quartile: Q2 Rank in area: 62/135 (Ranking edition: SCIE)

SCImago Journal Rank

(Indicator corresponding to the last year available on this portal, year 2022)
  • Year 2022
  • SJR Journal Impact: 1.095
  • Best Quartile: Q1
  • Area: Physiology Quartile: Q1 Rank in area: 42/194
  • Area: Immunology and Microbiology (miscellaneous) Quartile: Q1 Rank in area: 18/73
  • Area: Ecology Quartile: Q1 Rank in area: 53/449
  • Area: Microbiology (medical) Quartile: Q1 Rank in area: 31/128
  • Area: Infectious Diseases Quartile: Q1 Rank in area: 78/324
  • Area: Cell Biology Quartile: Q2 Rank in area: 110/289
  • Area: Genetics Quartile: Q2 Rank in area: 94/351

Scopus CiteScore

(Indicator corresponding to the last year available on this portal, year 2022)
  • Year 2022
  • CiteScore of the Journal : 2.4
  • Area: Ecology Percentile: 51
  • Area: Immunology and Microbiology (all) Percentile: 38
  • Area: Infectious Diseases Percentile: 36
  • Area: Microbiology (medical) Percentile: 29
  • Area: Physiology Percentile: 20
  • Area: Genetics Percentile: 20
  • Area: Cell Biology Percentile: 12

Journal Citation Indicator (JCI)

(Indicator corresponding to the last year available on this portal, year 2022)
  • Year 2022
  • Journal Citation Indicator (JCI): 0.93
  • Best Quartile: Q2
  • Area: MICROBIOLOGY Quartile: Q2 Rank in area: 48/156

Dimensions

(Data updated as of 19-01-2024)
  • Total citations: 1
  • Recent citations (2 years): 1

Abstract

Mitogen-activated protein kinase (MAPK) pathways regulate essential processes in eukaryotes. However, since uncontrolled activation of these cascades has deleterious effects, precise negative regulation of signaling flow through them, mainly executed by protein phosphatases, is crucial. Previous studies showed that the absence of Ptc1 protein phosphatase results in the upregulation of the MAPK of the cell wall integrity (CWI) pathway, Slt2, and numerous functional defects in Saccharomyces cerevisiae, including a failure to undergo cell separation under heat stress. In this study, we demonstrate that multibudded ptc1Δ cells also exhibit impaired mitochondrial inheritance and that excessive Slt2 kinase activity is responsible for their growth deficiency and daughter-specific G1 cell cycle arrest, as well as other physiological alterations, namely, mitochondrial hyperpolarization and reactive oxygen species (ROS) accumulation. We bring to light the fact that sustained Slt2 kinase activity inhibits signaling through the Sch9 branch of the TORC1 pathway in ptc1Δ cells, leading to increased autophagy. After cytokinesis, septin rings asymmetrically disassembled in ptc1Δ multibudded cells, abnormally remaining at the daughter cell side and eventually relocalizing at the daughter cell periphery, where they occasionally colocalized with the autophagic protein Atg9. Finally, we show that the inability of ptc1Δ cells to undergo cell separation is not due to a failure in the regulation of Ace2 and morphogenesis (RAM) pathway, since the transcription factor Ace2 correctly enters the daughter cell nuclei. However, the Ace2-regulated endochitinase Cts1 did not localize to the septum, preventing the proper degradation of this structure.IMPORTANCE This study provides further evidence that the cell cycle is regulated by complex signaling networks whose purpose is to guarantee a robust response to environmental threats. Using the S. cerevisiae eukaryotic model, we show that, under the stress conditions that activate the CWI MAPK pathway, the absence of the protein phosphatase Ptc1 renders Slt2 hyperactive, leading to numerous physiological alterations, including perturbed mitochondrial inheritance, oxidative stress, changes in septin dynamics, increased autophagy, TORC1-Sch9 inhibition, and ultimately cell cycle arrest and the failure of daughter cells to separate, likely due to the absence of key degradative enzymes at the septum. These results imply novel roles for the CWI pathway and unravel new cell cycle-regulatory controls that operate beyond the RAM pathway, arresting buds in G1 without compromising further division rounds in the mother cell.

Funding information

Funders

Bibliographic References

  • 10.3390/ijms21030709
  • 10.1126/science.2683079
  • 10.3390/cells11040704
  • 10.1111/mmi.14387
  • 10.1128/MCB.00403-10
  • 10.1016/s0092-8674(01)00596-7
  • 10.1016/S0021-9258(18)55057-2
  • 10.1128/JB.180.19.5030-5037.1998
  • 10.1128/MMBR.00038-05
  • 10.3389/fcell.2016.00119
  • 10.3389/fcell.2021.793920
  • 10.1016/j.bbamcr.2007.05.003
  • 10.3390/ijms22031110
  • 10.3390/ijms23031791
  • 10.1007/s10123-019-00092-2
  • 10.3390/jof8040368
  • 10.4161/auto.7.12.17971
  • 10.3390/jof7121041
  • 10.3390/ijms20071709
  • 10.15698/mic2019.05.677
  • 10.1007/BF02191592
  • 10.1038/sj.emboj.7601319
  • 10.1128/MCB.21.1.51-60.2001
  • 10.1534/genetics.115.183202
  • 10.1242/jcs.077065
  • 10.1038/nature08946
  • 10.1091/mbc.E18-12-0793
  • 10.1074/jbc.M607919200
  • 10.1091/mbc.e09-06-0532
  • 10.1128/MCB.01740-08
  • 10.1007/978-1-61779-173-4_18
  • Sánchez-Adriá IE, Sanmartín G, Prieto JA, Estruch F, Randez-Gil F. 2022. Slt2 is required to activate ER-stress-protective mechanisms through TORC1 inhibition and hexosamine pathway activation. J Fungi (Basel) 8.
  • 10.1128/mcb.14.6.3634-3645.1994
  • 10.4161/cc.1.2.114
  • 10.1242/jcs.180190
  • 10.1128/MCB.15.10.5740
  • 10.1128/MCB.21.19.6515-6528.2001
  • 10.1074/jbc.M115.683680
  • 10.1091/mbc.9.4.917
  • 10.1016/S0074-7696(08)62397-9
  • 10.1016/B978-0-12-385493-3.00007-3
  • 10.1016/j.tibs.2010.07.007
  • 10.4161/auto.7.12.18424
  • 10.3390/biom7030052
  • 10.1091/mbc.e07-05-0485
  • 10.1016/j.molcel.2007.04.020
  • 10.4161/cc.8.2.7381
  • 10.1242/jcs.209098
  • 10.1016/S0960-9822(02)01186-7
  • 10.1534/genetics.112.145516
  • 10.1101/gad.6.1.93
  • 10.1083/jcb.200203094
  • 10.1091/mbc.E10-02-0174
  • 10.1128/EC.00376-08
  • 10.1083/jcb.126.6.1361
  • 10.1016/j.cub.2009.08.041
  • 10.1016/j.devcel.2013.12.009
  • 10.1091/mbc.E13-09-0550
  • 10.1111/febs.16138
  • 10.1038/ncomms9256
  • 10.4014/jmb.1806.06014
  • 10.4161/auto.5.5.8091
  • 10.1016/j.cellsig.2019.109344
  • 10.1074/jbc.M205408200
  • 10.1091/mbc.E10-03-0182
  • 10.1016/j.celrep.2021.110149
  • 10.1091/mbc.01-10-0512
  • 10.1091/mbc.E17-09-0553
  • 10.1016/j.jmb.2021.167326
  • 10.1101/gad.318709.118
  • 10.1371/journal.pbio.0060203
  • 10.1083/jcb.201805100
  • 10.3390/jof4010001
  • 10.1534/genetics.117.1124
  • 10.3389/fimmu.2021.668602
  • 10.1002/(SICI)1097-0061(19980130)14:2%3C115::AID-YEA204%3E3.0.CO;2-2
  • 10.1534/genetics.115.176495
  • 10.1016/j.cell.2005.08.031
  • 10.15252/msb.20145606
  • 10.1002/yea.1291
  • 10.1038/nbt1037
  • 10.1038/nmeth.2413
  • 10.1016/0076-6879(91)94022-5
  • 10.1083/jcb.201005134
  • 10.1016/0022-2836(81)90438-1
  • 10.1093/emboj/20.21.5971