Universität zu Köln

Isensee, Joerg ORCID: 0000-0002-3390-0051, Schild, Cosimo, Schwede, Frank ORCID: 0000-0002-8185-3392 and Hucho, Tim ORCID: 0000-0002-4147-9308 (2017). Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive neurons and is maintained during aging. J. Cell Sci., 130 (13). S. 2134 - 2147. CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9137

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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)-RII beta (also known as PRKAR2B) and CaMKIIa (also known as CAMK2A) developed at around postnatal day 10, the time of nociceptor maturation. The integrative nociceptor marker, PKARII beta, allowed subgroup segregation earlier than could be achieved by assessing the classical markers TRPV1 and Na(v)1.8 (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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Isensee, Joerg UNSPECIFIED orcid.org/0000-0002-3390-0051 UNSPECIFIED Schild, Cosimo UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwede, Frank UNSPECIFIED orcid.org/0000-0002-8185-3392 UNSPECIFIED Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225736
DOI:	10.1242/jcs.197327
Journal or Publication Title:	J. Cell Sci.
Volume:	130
Number:	13
Page Range:	S. 2134 - 2147
Date:	2017
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9137
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-KINASE-II; ROOT GANGLION NEURONS; LONG-TERM-MEMORY; MAP KINASE; MOLECULAR-MECHANISMS; SODIUM-CHANNELS; GENE-EXPRESSION; DISTINCT PHASES; CHRONIC PAIN; CELL Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22573