title: Hsp90 nuclear accumulation in quiescence is linked to chaperone function and spore development in yeast.
abstract: The 90-kDa heat-shock protein (Hsp90) operates in the context of a multichaperone complex to promote maturation of nuclear and cytoplasmic clients. We have discovered that Hsp90 and the cochaperone Sba1/p23 accumulate in the nucleus of quiescent Saccharomyces cerevisiae cells. Hsp90 nuclear accumulation was unaffected in sba1Delta cells, demonstrating that Hsp82 translocates independently of Sba1. Translocation of both chaperones was dependent on the alpha/beta importin SRP1/KAP95. Hsp90 nuclear retention was coincident with glucose exhaustion and seems to be a starvation-specific response, as heat shock or 10% ethanol stress failed to elicit translocation. We generated nuclear accumulation-defective HSP82 mutants to probe the nature of this targeting event and identified a mutant with a single amino acid substitution (I578F) sufficient to retain Hsp90 in the cytoplasm in quiescent cells. Diploid hsp82-I578F cells exhibited pronounced defects in spore wall construction and maturation, resulting in catastrophic sporulation. The mislocalization and sporulation phenotypes were shared by another previously identified HSP82 mutant allele. Pharmacological inhibition of Hsp90 with macbecin in sporulating diploid cells also blocked spore formation, underscoring the importance of this chaperone in this developmental program.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Hugo
authors.initials: H
authors.lastname: Tapia
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Morano
mesh_terms: D000483:Alleles; D002467:Cell Nucleus / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013172:Spores, Fungal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D028901:alpha Karyopherins / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins; D005947:Glucose