title: The yeast tumor suppressor homologue Sro7p is required for targeting of the sodium pumping ATPase to the cell surface.
abstract: The SRO7/SOP1 encoded tumor suppressor homologue of Saccharomyces cerevisiae is required for maintenance of ion homeostasis in cells exposed to NaCl stress. Here we show that the NaCl sensitivity of the sro7Delta mutant is due to defective sorting of Ena1p, the main sodium pump in yeast. On exposure of sro7Delta mutants to NaCl stress, Ena1p fails to be targeted to the cell surface, but is instead routed to the vacuole for degradation via the multivesicular endosome pathway. SRO7-deficient mutants accumulate post-Golgi vesicles at high salinity, in agreement with a previously described role for Sro7p in late exocytosis. However, Ena1p is not sorted into these post-Golgi vesicles, in contrast to what is observed for the vesicles that accumulate when exocytosis is blocked in sec6-4 mutants at high salinity. These observations imply that Sro7p has a previously unrecognized role for sorting of specific proteins into the exocytic pathway. Screening for multicopy suppressors identified RSN1, encoding a transmembrane protein of unknown function. Overexpression of RSN1 restores NaCl tolerance of sro7Delta mutants by retargeting Ena1p to the plasma membrane. We propose a model in which blocked exocytic sorting in sro7Delta mutants, gives rise to quality control-mediated routing of Ena1p to the vacuole.
authors.affiliation: Department of Cell and Molecular Biology, Microbiology, Göteborg University, SE-405 30 Göteborg, Sweden. ingrid.wadskog@ing.hj.se
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wadskog
authors.forename: Annabelle
authors.initials: A
authors.lastname: Forsmark
authors.forename: Guendalina
authors.initials: G
authors.lastname: Rossi
authors.forename: Catherine
authors.initials: C
authors.lastname: Konopka
authors.forename: Mattias
authors.initials: M
authors.lastname: Oyen
authors.forename: Mattias
authors.initials: M
authors.lastname: Goksör
authors.forename: Hans
authors.initials: H
authors.lastname: Ronne
authors.forename: Patrick
authors.initials: P
authors.lastname: Brennwald
authors.forename: Lennart
authors.initials: L
authors.lastname: Adler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005800:Genes, Fungal; D006056:Golgi Apparatus / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000187:drug effects; D017385:Sequence Homology; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase; D013816:Thermodynamics; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D027682:Cation Transport Proteins; C086375:ENA1 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; C116430:SRO7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D012965:Sodium Chloride; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase