Abstract
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
g
lucose-
i
nsensitive
t
ranscription (
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°, 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.