PMID:28515230

Citation	Isensee, J, Schild, C, Schwede, F and Hucho, T (2017) Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive neurons and is maintained during aging. J. Cell. Sci. 130:2134-2146
Abstract	Maturation of nociceptive neurons depends on changes in transcription factors, ion channels and neuropeptides. Mature nociceptors initiate pain in part by drastically reducing the activation threshold via intracellular sensitization signaling. Whether sensitization signaling also changes during development and aging remains so far unknown. Using a novel automated microscopy approach, we quantified changes in intracellular signaling protein expression and in their signaling dynamics, as well as changes in intracellular signaling cascade wiring, in sensory neurons from newborn to senescent (24 months of age) rats. We found that nociceptive subgroups defined by the signaling components protein kinase A (PKA)-RIIβ (also known as PRKAR2B) and CaMKIIα (also known as CAMK2A) developed at around postnatal day 10, the time of nociceptor maturation. The integrative nociceptor marker, PKA-RIIβ, allowed subgroup segregation earlier than could be achieved by assessing the classical markers TRPV1 and Na1.8 (also known as SCN10A). Signaling kinetics remained constant over lifetime despite in part strong changes in the expression levels. Strikingly, we found a mechanism important for neuronal memory - i.e. the crosstalk from cAMP and PKA to ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) - to emerge postnatally. Thus, maturation of nociceptors is closely accompanied by altered expression, activation and connectivity of signaling pathways known to be central for pain sensitization and neuronal memory formation.
Links	PubMed Online version:10.1242/jcs.197327
Keywords	Aging/genetics; Animals; Animals, Newborn/genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics; Cyclic AMP/genetics; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/genetics; Ganglia, Spinal/metabolism; MAP Kinase Signaling System/genetics; NAV1.8 Voltage-Gated Sodium Channel/genetics; Nociceptors/metabolism; Rats; Sensory Receptor Cells/metabolism; TRPV Cation Channels/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:MK01	involved_in	GO:0007568: aging	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RAT:MK03	involved_in	GO:0007568: aging	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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