Originally published as Genetics Published Articles Ahead of Print on September 2, 2005.

Genetics, Vol. 171, 1523-1533, December 2005, Copyright © 2005
doi:10.1534/genetics.105.047233

Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling

Lili Wang, Kenneth Griffiths, Jr.¹, Y. Hi Zhang, F. Douglas Ivey and Charles S. Hoffman²

Biology Department, Boston College, Chestnut Hill, Massachusetts 02467

² Corresponding author: Biology Department, Boston College, Higgins Hall 401B, 140 Commonwealth Ave., Chestnut Hill, MA 02467.
E-mail: hoffmacs{at}bc.edu

Mutations affecting the Schizosaccharomyces pombe cAMP phosphodiesterase (PDE) gene cgs2⁺ were identified in a screen for suppressors of mutant alleles of the adenylate cyclase gene (git2⁺/cyr1⁺), which encode catalytically active forms of the enzyme that cannot be stimulated by extracellular glucose signaling. These mutations suppress both the git2^– mutant alleles used in the suppressor selection and mutations in git1⁺, git3⁺, git5⁺, git7⁺, git10⁺, and git11⁺, which are all required for adenylate cyclase activation. Notably, these cgs2 mutant alleles fail to suppress mutations in gpa2⁺, which encodes the G subunit of a heterotrimeric G protein required for adenylate cyclase activation, although the previously identified cgs2-2 allele does suppress loss of gpa2⁺. Further analysis of the cgs2-s1 allele reveals a synthetic interaction with the gpa2^R176H-activated allele, with respect to derepression of fbp1-lacZ transcription in glucose-starved cells. In addition, direct measurements of cAMP levels show that cgs2-s1 cells maintain normal basal cAMP levels, but are severely defective in feedback regulation upon glucose detection. These results suggest that PDE activity in S. pombe may be coordinately regulated with adenylate cyclase activity as part of the feedback regulation mechanism to limit the cAMP response to glucose detection.

This article has been cited by other articles:

				M. A. Alaamery and C. S. Hoffman Schizosaccharomyces pombe Hsp90/Git10 Is Required for Glucose/cAMP Signaling Genetics, April 1, 2008; 178(4): 1927 - 1936. [Abstract] [Full Text] [PDF]

				F. D. Ivey, L. Wang, D. Demirbas, C. Allain, and C. S. Hoffman Development of a Fission Yeast-Based High-Throughput Screen to Identify Chemical Regulators of cAMP Phosphodiesterases J Biomol Screen, January 1, 2008; 13(1): 62 - 71. [Abstract] [PDF]

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