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Mtl1 O-mannosylation mediated by both Pmt1 and Pmt2 is important for cell survival under oxidative conditions and TOR

Mima Ivanova Petkova1, Nuria Pujol-Carrion, Maria Angeles de la Torre-Ruiz

  • 1Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universidad de Lleida, Lleida 25008, Spain.

Fungal Genetics and Biology : FG & B
|September 11, 2012
PubMed

Insights

O-mannosylation of Mtl1 protein is crucial for cell survival during oxidative stress and nutrient starvation. This modification by Pmt1 and Pmt2 enhances Mtl1 stability and is vital for the cell wall integrity pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mtl1 is a cell surface sensor involved in the Pkc1-MAPK pathway, responding to oxidative stress and nutrient starvation.
  • Mtl1 interacts with Rom2, a Guanine nucleotide Exchange Factor (GEF) in the Cell Wall Integrity (CWI) pathway.
  • Mtl1 is an N-glycosylated protein, extensively O-mannosylated by Pmt1, Pmt4, and predominantly Pmt2.

Purpose of the Study:

  • To investigate the role of Mtl1 O-mannosylation in cellular responses to stress.
  • To elucidate the impact of O-mannosylation deficiency on Mtl1 localization and function.
  • To understand the relationship between Mtl1, O-mannosylation, and the Pkc1-MAPK pathway.

Main Methods:

  • Analysis of Mtl1 localization in wild-type and O-mannosylation-deficient mutants (pmt1, pmt2).
  • Assessment of cell survival under oxidative stress and TOR blockade (rapamycin treatment).
  • Measurement of Slt2 kinase activity in response to rapamycin.
  • Analysis of Mtl1 gene expression under quiescent conditions.

Main Results:

  • O-mannosylation of Mtl1 is essential for cell survival during oxidative stress and TOR blockade.
  • Deficiency in O-mannosylation (pmt1, pmt2 mutants) disrupts Mtl1 localization at the septum and shmoo tip.
  • Slt2 activity is impaired in pmt2 and mtl1 mutants upon rapamycin treatment.
  • Mtl1 is transcriptionally upregulated during quiescence, and O-mannosylation by Pmt1/Pmt2 enhances Mtl1 stability.

Conclusions:

  • Mtl1 O-mannosylation, particularly by Pmt1 and Pmt2, is critical for cellular responses to oxidative stress and rapamycin treatment.
  • Proper O-mannosylation ensures correct Mtl1 localization and protein stability, contributing to cell survival.
  • Mtl1 O-mannosylation plays a significant role in maintaining cell wall integrity and stress response pathways.

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