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Nociceptive tuning by stem cell factor/c-Kit signaling

Official URL:https://doi.org/10.1016/j.neuron.2007.10.040
PubMed:View item in PubMed
Creators Name:Milenkovic, N. and Frahm, C. and Gassmann, M. and Griffel, C. and Erdmann, B. and Birchmeier, C. and Lewin, G.R. and Garratt, A.N.
Journal Title:Neuron
Journal Abbreviation:Neuron
Volume:56
Number:5
Page Range:893-906
Date:6 December 2007
Keywords:Molneuro, Sysbio, Signaling, Animals, Mice
Abstract:The molecular mechanisms regulating the sensitivity of sensory circuits to environmental stimuli are poorly understood. We demonstrate here a central role for stem cell factor (SCF) and its receptor, c-Kit, in tuning the responsiveness of sensory neurons to natural stimuli. Mice lacking SCF/c-Kit signaling displayed profound thermal hypoalgesia, attributable to a marked elevation in the thermal threshold and reduction in spiking rate of heat-sensitive nociceptors. Acute activation of c-Kit by its ligand, SCF, resulted in a reduced thermal threshold and potentiation of heat-activated currents in isolated small-diameter neurons and thermal hyperalgesia in mice. SCF-induced thermal hyperalgesia required the TRP family cation channel TRPV1. Lack of c-Kit signaling during development resulted in hypersensitivity of discrete mechanoreceptive neuronal subtypes. Thus, c-Kit can now be grouped with a small family of receptor tyrosine kinases, including c-Ret and TrkA, that control the transduction properties of sensory neurons.
ISSN:0896-6273
Publisher:Cell Press (U.S.A.)
Item Type:Article

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