title: Mutations that affect vacuole biogenesis inhibit proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae.
abstract: In yeast, increased levels of the sterol biosynthetic enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase isozyme, Hmg1p, induce assembly of nuclear-associated ER membranes called karmellae. To identify additional genes involved in karmellae assembly, we screened temperature-sensitive mutants for karmellae assembly defects. Two independently isolated, temperature-sensitive strains that were also defective for karmellae biogenesis carried mutations in VPS16, a gene involved in vacuolar protein sorting. Karmellae biogenesis was defective in all 13 other vacuole biogenesis mutants tested, although the severity of the karmellae assembly defect varied depending on the particular mutation. The hypersensitivity of 14 vacuole biogenesis mutants to tunicamycin was well correlated with pronounced defects in karmellae assembly, suggesting that the karmellae assembly defect reflected alteration of ER structure or function. Consistent with this hypothesis, seven of eight mutations causing defects in secretion also affected karmellae assembly. However, the vacuole biogenesis mutants were able to proliferate their ER in response to Hmg2p, indicating that the mutants did not have a global defect in the process of ER biogenesis.
authors.affiliation: Department of Zoology, University of Washington, Seattle, Washington 98195-1800, USA.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Koning
authors.forename: Lynnelle L
authors.initials: LL
authors.lastname: Larson
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Cadera
authors.forename: Mark L
authors.initials: ML
authors.lastname: Parrish
authors.forename: Robin L
authors.initials: RL
authors.lastname: Wright
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000502:physiology* / Q000648:ultrastructure; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D024261:HMGB2 Protein / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D014617:Vacuoles / Q000502:physiology* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins
chemical_list: D000900:Anti-Bacterial Agents; D005656:Fungal Proteins; D024243:HMGB1 Protein; D024261:HMGB2 Protein; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C080045:VPS16 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D014415:Tunicamycin; D006903:Hydroxymethylglutaryl CoA Reductases