title: Formation and dissociation of proteasome storage granules are regulated by cytosolic pH.
abstract: The 26S proteasome is the major protein degradation machinery of the cell and is regulated at many levels. One mode of regulation involves accumulation of proteasomes in proteasome storage granules (PSGs) upon glucose depletion. Using a systematic robotic screening approach in yeast, we identify trans-acting proteins that regulate the accumulation of proteasomes in PSGs. Our dataset was enriched for subunits of the vacuolar adenosine triphosphatase (V-ATPase) complex, a proton pump required for vacuole acidification. We show that the impaired ability of V-ATPase mutants to properly govern intracellular pH affects the kinetics of PSG formation. We further show that formation of other protein aggregates upon carbon depletion also is triggered in mutants with impaired activity of the plasma membrane proton pump and the V-ATPase complex. We thus identify cytosolic pH as a specific cellular signal involved both in the glucose sensing that mediates PSG formation and in a more general mechanism for signaling carbon source exhaustion.
authors.affiliation: The Nano Center, Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Lee Zeev
authors.initials: LZ
authors.lastname: Peters
authors.forename: Rotem
authors.initials: R
authors.lastname: Hazan
authors.forename: Michal
authors.initials: M
authors.lastname: Breker
authors.forename: Maya
authors.initials: M
authors.lastname: Schuldiner
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Aroya
mesh_terms: D003594:Cytoplasmic Granules / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology*; D059748:Proteolysis; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D005656:Fungal Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D025262:Vacuolar Proton-Translocating ATPases; D005947:Glucose