[Physiopathology of cAMP/PKA signaling in neurons].
Cyclic adenosine monophosphate (cAMP) and the cyclic-AMP dependent protein kinase (PKA) regulate a plethora of cellular functions in virtually all eukaryotic cells. In neurons, the cAMP/PKA signaling cascade controls a number of biological properties such as axonal growth, synaptic transmission, regulation of excitability or long term changes in the nucleus. Genetically-encoded optical biosensors for cAMP or PKA considerably improved our understanding of these processes by providing a real-time measurement in living neurons. In this review, we describe the recent progresses made in the creation of biosensors for cAMP or PKA activity. These biosensors revealed profound differences in the amplitude of the cAMP signal evoked by neuromodulators between various neuronal preparations. These responses can be resolved at the level of individual neurons, also revealing differences related to the neuronal type. At the subcellular level, biosensors reported different signal dynamics in domains like dendrites, cell body, nucleus and axon. Combining this imaging approach with pharmacology or genetical models points at phosphodiesterases and phosphatases as critical regulatory proteins. Biosensor imaging will certainly help understand the mechanism of action of current drugs as well as help in devising novel therapeutic strategies for neuropsychiatric diseases.
Liliana
L
Castro
Cedric
C
Yapo
Pierre
P
Vincent
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D004298:Dopamine