Schizosaccharomyces pombe Hsp90/Git10 is required for glucose/cAMP signaling.
The fission yeast Schizosaccharomyces pombe senses environmental glucose through a cAMP-signaling pathway. Elevated cAMP levels activate protein kinase A (PKA) to inhibit transcription of genes involved in sexual development and gluconeogenesis, including the fbp1(+) gene, which encodes fructose-1,6-bisphosphatase. Glucose-mediated activation of PKA requires the function of nine glucose-insensitive transcription (git) genes, encoding adenylate cyclase, the PKA catalytic subunit, and seven "upstream" proteins required for glucose-triggered adenylate cyclase activation. We describe the cloning and characterization of the git10(+) gene, which is identical to swo1(+) and encodes the S. pombe Hsp90 chaperone protein. Glucose repression of fbp1(+) transcription is impaired by both git10(-) and swo1(-) mutant alleles of the hsp90(+) gene, as well as by chemical inhibition of Hsp90 activity and temperature stress to wild-type cells. Unlike the swo1(-) mutant alleles, the git10-201 allele supports cell growth at 37 degrees , while severely reducing glucose repression of an fbp1-lacZ reporter, suggesting a separation-of-function defect. Sequence analyses of three swo1(-) alleles and the one git10(-) allele indicate that swo1(-) mutations alter core functional domains of Hsp90, while the git10(-) mutation affects the Hsp90 central domain involved in client protein binding. These results suggest that Hsp90 plays a specific role in the S. pombe glucose/cAMP pathway.
Alaamery
Manal A
MA
Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Hoffman
Charles S
CS
D000483:Alleles; D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism*; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D005947:Glucose / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D018869:Heat-Shock Response; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013696:Temperature; D001616:beta-Galactosidase / Q000378:metabolism
D018841:HSP90 Heat-Shock Proteins; D029702:Schizosaccharomyces pombe Proteins; C091275:Swo1 protein, S pombe; D000242:Cyclic AMP; D001616:beta-Galactosidase; D005947:Glucose