title: Mtl1 O-mannosylation mediated by both Pmt1 and Pmt2 is important for cell survival under oxidative conditions and TOR blockade.
abstract: Mtl1 is a cell surface sensor and member of the Pkc1-MAPK pathway that senses oxidative stress and nutrient starvation. Here we demonstrate that the Mtl1 cytoplasmic domain physically interacts with the GEF (GTPase Exchange Factor) protein Rom2 of the CWI (Cell wall Integrity) pathway. Mtl1 is N-glycosylated protein, highly O-mannosylated by Pmt1, Pmt4 and mostly by Pmt2. Mtl1 localises to the bud, septum, the tip of the shmoo and the cell periphery. The O-mannosylation deficiency that occurs in both the pmt1 and pmt2 mutants adversely affects the distribution of Mtl1 on the septum and also hinders Mtl1 localisation in the tip of the shmoo. Here we present results demonstrating that: (i) O-mannosylation and, more specifically that affecting Mtl1 protein is required for cell survival in response to both oxidative stress and TOR blockade; (ii) Slt2 activity is impaired upon rapamycin treatment in both pmt2 and mtl1 mutants; (iii) Mtl1 is transcriptionally upregulated in quiescent conditions, (iv) O-mannosylation mediated by Pmt1 and Pmt2 favours Mtl1 protein stability. We propose a relevant role for Mtl1 O-mannosylation mediated by both Pmt1 and Pmt2 in the response to oxidative stress and in rapamycin treatment.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universidad de Lleida, Lleida 25008, Spain.
authors.forename: Mima Ivanova
authors.initials: MI
authors.lastname: Petkova
authors.forename: Nuria
authors.initials: N
authors.lastname: Pujol-Carrion
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: de la Torre-Ruiz
mesh_terms: D000595:Amino Acid Sequence; D015966:Gene Expression Regulation, Fungal; D006031:Glycosylation; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C550933:Mtl1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins