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cGMP-mediated signaling via cGKI{alpha}s required for the guidance and connectivity of sensory axons

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Official URL:https://doi.org/10.1083/jcb.200207058
PubMed:View item in PubMed
Creators Name:Schmidt, H. and Werner, M. and Heppenstall, P.A. and Henning, M. and More, M.I. and Kuehbandner, S. and Lewin, G.R. and Hofmann, F. and Feil, R. and Rathjen, F.G.
Journal Title:Journal of Cell Biology
Journal Abbreviation:J Cell Biol
Page Range:489-498
Date:11 November 2002
Keywords:cGMP Signaling, Axonal Pathfinding, cGMP-Dependent Protein Kinase I, Sensory Axons, Nociceptive Flexion Reflex
Abstract:Previous in vitro studies using cGMP or cAMP revealed a cross-talk between signaling mechanisms activated by axonal guidance receptors. However, the molecular elements modulated by cyclic nucleotides in growth cones are not well understood. cGMP is a second messenger with several distinct targets including cGMP-dependent protein kinase I (cGKI). Our studies indicated that the alpha isoform of cGKI is predominantly expressed by sensory axons during developmental stages, whereas most spinal cord neurons are negative for cGKI. Analysis of the trajectories of axons within the spinal cord showed a longitudinal guidance defect of sensory axons within the developing dorsal root entry zone in the absence of cGKI. Consequently, in cGKI-deficient mice, fewer axons grow within the dorsal funiculus of the spinal cord, and lamina-specific innervation, especially by nociceptive sensory neurons, is strongly reduced as deduced from anti-trkA staining. These axon guidance defects in cGKI-deficient mice lead to a substantial impairment in nociceptive flexion reflexes, shown using electrophysiology. In vitro studies revealed that activation of cGKI in embryonic dorsal root ganglia counteracts semaphorin 3A-induced growth cone collapse. Our studies therefore reveal that cGMP signaling is important for axonal growth in vivo and in vitro.
Publisher:Rockefeller University Press (U.S.A.)
Additional Information:Copyright (c) 2002 by The Rockefeller University Press
Item Type:Article

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