title: The signaling pathways underlying starvation-induced upregulation of α-mannosidase Ams1 in Saccharomyces cerevisiae.
abstract: BACKGROUND
  Cells have evolved the mechanisms to survive nutritional shortages in the environment. In Saccharomyces cerevisiae, α-mannosidase Ams1 is known to play a role in catabolism of N-linked free oligosaccharides in the cytosol. Although, this enzyme is also known to be transported selectively from the cytosol to the vacuoles by autophagy, the physiological significance of this transport has not been clarified.
  
  
  METHODS
  To elucidate the regulatory mechanism of the activity of Ams1, we assessed the enzymatic activity of the cell free extract of the wild-type and various gene disruptants under different nutritional conditions. In addition, the regulation of Ams1 at both transcription and post-translation was examined.
  
  
  RESULTS
  The activity of Ams1 was significantly increased upon the depletion of glucose in the medium. Interestingly, the activity of the enzyme was also stimulated by nitrogen starvation. Our data showed that the activity of Ams1 is regulated by the stress responsive transcriptional factors Msn2/4 through the protein kinase A and the target of rapamycin complex 1 pathways. In addition, Ams1 is post-translationally activated by Pep4-dependent processing in the vacuoles.
  
  
  CONCLUSIONS
  Yeast cells monitor extracellular nutrients to regulate mannoside catabolism via the cellular signaling pathway.
  
  
  CONCLUSIONS
  This study revealed that intracellular Ams1 activity is exquisitely upregulated in response to nutrient starvation by induced expression as well as by Pep4-dependent enhanced activity in the vacuoles. The signaling molecules responsible for regulation of Ams1 were also clarified.
authors.affiliation: Department of Biotechnology, Faculty of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan. Electronic address: mumekawa@fc.ritsumei.ac.jp.
authors.forename: Midori
authors.initials: M
authors.lastname: Umekawa
authors.affiliation: Department of Biotechnology, Faculty of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ujihara
authors.affiliation: Department of Biotechnology, Faculty of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Makishima
authors.affiliation: Department of Biotechnology, Faculty of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takematsu
authors.affiliation: Department of Biotechnology, Faculty of Life Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Wakayama
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000502:physiology; D009584:Nitrogen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D015854:Up-Regulation; D043323:alpha-Mannosidase / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; D000076222:Mechanistic Target of Rapamycin Complex 1; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D043323:alpha-Mannosidase; C499267:PEP4 protein, S cerevisiae; D016282:Aspartic Acid Endopeptidases; D005947:Glucose; D009584:Nitrogen
keywords: Autophagy; Carbohydrate metabolism; Stress response