3′,5′-cyclic nucleotides (i.e., cAMP and cGMP) are intracellular signaling molecules that regulate a vast number of physiological processes, from cell-specific gene transcription to whole animal behavior (c.f., Neves et al. 2002; Francis et al. 2010). In order for cAMP and cGMP signaling to be effective, they must be tightly controlled. Although cyclic nucleotides are expressed in nearly every tissue, they are far from ubiquitously distributed. Cyclic nucleotides are actually confined to specific subcellular microdomains by a superfamily of enzymes known as the 3′,5′-cyclic nucleotide phosphodiesterases (PDEs) (Francis et al. 2011; Edwards et al. 2012). PDEs are the only known enzymes to degrade cyclic nucleotides (Francis et al. 2011). By hydrolyzing cAMP and cGMP, PDEs not only control the total cellular content of cAMP and cGMP, they are responsible for restricting these cyclic nucleotides to their microdomains. It is this compartmentalization of cyclic...
The author thanks Jennifer Klett for technical assistance with Fig. 2a, Baher Ibrahim for technical assistance with Fig. 2b, Neema Patel for technical assistance with Fig. 3b, and William Capell for technical assistance with Fig. 3c. This work was funded by 1R01MH101130 from NIMH and a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation (all awards to MPK).
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