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Spatiotemporal Dynamics and Regulation of cAMP and PKA in Early Stage Hippocampal Neurons
Author(s) -
Gorshkov Kirill,
Ramamurthy Santosh,
Mehta Sohum,
Ronnett Gabrielle V.,
Zhou Fengquan,
Zhang Jin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.869.8
Subject(s) - hippocampal formation , axon , protein kinase a , cyclic adenosine monophosphate , phosphodiesterase , axon guidance , neuroscience , microbiology and biotechnology , biology , chemistry , kinase , biochemistry , receptor , enzyme
Cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) are critical axon determinants that regulate neuronal polarity and axon formation, but the spatiotemporal dynamics of cAMP and PKA in developing neuronal subcompartments are poorly understood. Here, we use genetically encoded fluorescent biosensors to understand the compartmentalized dynamics of cAMP and PKA signaling in developing hippocampal neurons in vitro . In five‐day‐old hippocampal neurons, we detected an axon‐directed cAMP gradient dependent on phosphodiesterase activity and an axon‐directed PKA gradient dependent on the association of PKA with A‐kinase anchoring proteins (AKAPs). Furthermore, disrupting PKA anchoring to AKAPs in early hippocampal neurons leads to enhanced axon elongation. This effect is correlated with an enhancement of the stimulated axon‐directed cAMP and PKA gradients. We propose that a negative feedback loop in the cAMP/PKA/AKAP signaling microdomain plays an essential role in controlling the developmental program of hippocampal neurons. Support or Funding Information This work was supported by NIH RO1 DK073368 (to J.Z.), DGIST Convergence Science Center grant 11‐BD‐04 (to G.V.R), NSF GRF 1232825 (to K.G.).