title: A network of genes connects polyglutamine toxicity to ploidy control in yeast.
abstract: Neurodegeneration is linked to protein aggregation in several human disorders. In Huntington's disease, the length of a polyglutamine stretch in Huntingtin is correlated to neuronal death. Here we utilize a model based on glutamine stretches of 0, 30 or 56 residues in Saccharomyces cerevisiae to understand how such toxic proteins interfere with cellular physiology. A toxicity-mimicking cytostatic effect is evident from compromised colony formation upon expression of polyglutamines. Interestingly, diploid cells are insensitive to polyglutamines and haploid cells can escape cytostasis by hyperploidization. Using a genome-wide screen for genes required to obtain the cytostatic effect, we identify a network related to the budding process and cellular division. We observe a striking mislocalization of the septins Cdc10 and Shs1 in cells arrested by polyglutamines, suggesting that the septin ring may be a pivotal structure connecting polyglutamine toxicity and ploidy.
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM) and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.
authors.forename: Christoph J O
authors.initials: CJ
authors.lastname: Kaiser
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Grötzinger
authors.forename: Julia M
authors.initials: JM
authors.lastname: Eckl
authors.forename: Katharina
authors.initials: K
authors.lastname: Papsdorf
authors.forename: Stefan
authors.initials: S
authors.lastname: Jordan
authors.forename: Klaus
authors.initials: K
authors.lastname: Richter
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D015153:Blotting, Western; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019791:Guanidine / Q000494:pharmacology; D006238:Haploidy; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008957:Models, Genetic; D010455:Peptides / Q000633:toxicity*; D010641:Phenotype; D011003:Ploidies; D011328:Prions / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D058112:Septins / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D010455:Peptides; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; C097188:polyglutamine; D058112:Septins; D019791:Guanidine