title: Mutations that are synthetically lethal with a gas1Delta allele cause defects in the cell wall of Saccharomyces cerevisiae.
abstract: The GAS1-related genes of fungi encode GPI-anchored proteins with beta-1,3-glucanosyltransferase activity. Loss of this activity results in defects in the assembly of the cell wall. We isolated mutants that show a synthetic defect when combined with a gas1Delta allele in Saccharomyces cerevisiae, and identified nine wild-type genes that rescue this defect. The indispensability of BIG1 and KRE6 for the viability of gas1Delta cells confirmed the important role of beta-1,6-glucan in cells that are defective in the processing of beta-1,3-glucan. The identification of the Wsc1p hypo-osmotic stress sensor and components of the PKC signal transduction pathway in our screen also confirmed that the cell wall integrity response attenuates the otherwise lethal gas1Delta defect. Unexpectedly, we found that the KEX2 gene is also required for the viability of the gas1Delta mutant. Kex2p is a Golgi/endosome-membrane-anchored protease that processes secretory preproteins. A cell wall defect was also found in the kex2Delta mutant, which was suppressible by multiple copies of the MKC7 or YAP3 gene, both of which encode other GPI-anchored proteases. Therefore, normal cell wall assembly requires proteolytic processing of secretory preproteins. Furthermore, the genes CSG2 and IPT1 were found to be required for normal growth of gas1Delta cells in the presence of 1 M sorbitol. This finding suggests that complex sphingolipids play a role in the hyper-osmotic response.
authors.affiliation: Department of Biotechnology, University of Tokyo, Bunkyo-ku, 113-8657 Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tomishige
authors.forename: Y
authors.initials: Y
authors.lastname: Noda
authors.forename: H
authors.initials: H
authors.lastname: Adachi
authors.forename: H
authors.initials: H
authors.lastname: Shimoi
authors.forename: A
authors.initials: A
authors.lastname: Takatsuki
authors.forename: K
authors.initials: K
authors.lastname: Yoda
mesh_terms: D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D005804:Genes, Lethal; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D043484:Proprotein Convertases; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism
chemical_list: C066709:GAS1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D043484:Proprotein Convertases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae