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Phosphodiesterase Diversity and Signal Processing Within cAMP Signaling Networks

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Book cover Phosphodiesterases: CNS Functions and Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 17))

Abstract

A large number of neuromodulators activate G-protein coupled receptors (GPCRs) and mediate their cellular actions via the regulation of intracellular cAMP, the small highly diffusible second messenger. In fact, in the same neuron several different GPCRs can regulate cAMP with seemingly identical timecourses that give rise to distinct signaling outcomes, suggesting that cAMP does not have equivalent access to all its downstream effectors and may exist within defined intracellular pools or domains. cAMP compartmentalization is the process that allows the neuron to differentially interpret these various intracellular cAMP signals into cellular response. The molecular mechanisms that give rise to cAMP compartmentalization are not fully understood, but it is thought that phosphodiesterases (PDEs), the enzymes that degrade cAMP, significantly contribute to this process. PDEs, as the sole mechanism of signal termination for cAMP, hold great promise as therapeutic targets for pathologies that are due to the dysregulation of intracellular cAMP signaling. Due to their diverse catalytic activity, regulation and localization each PDE subtype expressed in a given neuron may have a distinct role on downstream signaling.

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Authors and Affiliations

  1. Departments of Pharmacology and Systems Therapeutics, Friedman Brain Institute, System Biology Center New York, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1215, New York, NY, 10029, USA

    Susana R. Neves-Zaph

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  1. Susana R. Neves-Zaph
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Correspondence to Susana R. Neves-Zaph .

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  1. Department of Behavioral Medicine and Psychiatry; Department of Physiology and Pharmacology; Institute of Pharmacology, West Virginia University Health Sciences Center; Taishan Medical University, Morgantown; Taian, China, West Virginia, USA

    Han-Ting Zhang

  2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo The State University of New York, Buffalo, New York, USA

    Ying Xu

  3. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo The State University of New York, Buffalo, New York, USA

    James M. O'Donnell

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Neves-Zaph, S.R. (2017). Phosphodiesterase Diversity and Signal Processing Within cAMP Signaling Networks. In: Zhang, HT., Xu, Y., O'Donnell, J. (eds) Phosphodiesterases: CNS Functions and Diseases. Advances in Neurobiology, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-58811-7_1

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