A Uniform Extracellular Stimulus Triggers Distinct cAMP Signals in Different Compartments of a Simple Cell

cAMP, the classical second messenger, regulates many diverse cellular functions. The primary effector of cAMP signals, protein kinase A, differentially phosphorylates hundreds of cellular targets. Little is known, however, about the spatial and temporal nature of cAMP signals and their information c...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-11, Vol.98 (23), p.13049-13054
Main Authors: Rich, Thomas C., Fagan, Kent A., Tse, Tonia E., Schaack, Jerome, Dermot M. F. Cooper, Karpen, Jeffrey W.
Format: Article
Language:English
Subjects:
1-Methyl-3-isobutylxanthine - pharmacology
Alprostadil - pharmacology
Biological Sciences
Calcium - metabolism
Calibration
Cell Compartmentation
Cell Line
Cell membranes
Cells
Cellular biology
Cyclic AMP - metabolism
Cytosol
Enzymes
Fluorescence
Humans
Ion Transport
Kidney - cytology
Kidney - drug effects
Kidney - metabolism
Kidney cells
Neurons
Neutrophils
Patch-Clamp Techniques
Physiological regulation
Pipettes
Prostaglandins
Proteins
Signal Transduction
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Summary:cAMP, the classical second messenger, regulates many diverse cellular functions. The primary effector of cAMP signals, protein kinase A, differentially phosphorylates hundreds of cellular targets. Little is known, however, about the spatial and temporal nature of cAMP signals and their information content. Thus, it is largely unclear how cAMP, in response to different stimuli, orchestrates such a wide variety of cellular responses. Previously, we presented evidence that cAMP is produced in subcellular compartments near the plasma membrane, and that diffusion of cAMP from these compartments to the bulk cytosol is hindered. Here we report that a uniform extracellular stimulus initiates distinct cAMP signals within different cellular compartments. By using cyclic nucleotidegated ion channels engineered as cAMP biosensors, we found that prostaglandin E1stimulation of human embryonic kidney cells caused a transient increase in cAMP concentration near the membrane. Interestingly, in the same time frame, the total cellular cAMP rose to a steady level. The decline in cAMP levels near the membrane was prevented by pretreatment with phosphodiesterase inhibitors. These data demonstrate that spatially and temporally distinct cAMP signals can coexist within simple cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.221381398