How does cAMP control gene expression? We propose to test our main hypothesis that extracellular cAMP regulates gene expression in Dictyostelium by the same cell surface receptor which mediates chemotaxis. The hypothesis states than transmembrane signal transduction then causes the synthesis of intracellular second messengers which affect chemotaxis and gene expression by divergent pathways. The expression of a few known genes such as the uridine diphosphoglucose pyrophosphorylase (UDPGP) gene and many other unknown genes is regulated by exogenous cAMP. Mutants defective in UDPGP fail to complete the developmental cycle. We propose to define the pathways which result in expression of the cAMP regulated genes. Our experiments will exploit mutants defective in UDPGP, mutants defective in the cAMP chemosensory system, antibodies to the cAMP cell surface receptor and biochemicals which perturb second messengers. We have cloned and sequenced the UDPGP-1 gene and characterized its expression. Our hypothesis is based on the observation that the pharmacological specificity of the receptor which mediates the expression of this and other genes is indistinguishable from that of the cell surface receptor by which extracellular cAMP mediates chemotaxis. Our analysis will require definition of the cis acting regulatory sequences through which cAMP controls gene expression. It will be aided by the identification of suppressor mutants which may restore UDPGP synthesis and activity. If our hypothesis is correct, our experiments will elucidate transmembrane signal transduction, which leads to gene expression. Otherwise, they will still help to identify the pathway by which an extracellular signal leads to gene expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM027310-11
Application #
3274729
Study Section
Biochemistry Study Section (BIO)
Project Start
1987-07-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Hunter College
Department
Type
Schools of Arts and Sciences
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065