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Developmental regulation of sensory neurite growth by the tumor necrosis factor superfamily member LIGHT

Gavalda, Nuria, Gutierrez, Humberto and Davies, Alun M. 2009. Developmental regulation of sensory neurite growth by the tumor necrosis factor superfamily member LIGHT. Journal of Neuroscience 29 (6) , pp. 1599-1607. 10.1523/JNEUROSCI.3566-08.2009

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Abstract

In a PCR screen to identify novel cytokine candidates involved in neuronal development, we identified transcripts for the tumor necrosis factor superfamily member 14 (TNFSF14), generally known as LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), together with its receptors, lymphotoxin-β receptor (LTβR) and TNF family receptor herpesvirus entry mediator (HVEM), in the experimentally tractable sensory neurons of the mouse nodose ganglion. Immunocytochemistry revealed coexpression of LIGHT and its receptors in all nodose ganglion neurons in neonates. Enhancing LIGHT signaling in these neurons by overexpressing LIGHT inhibited BDNF-promoted neurite growth during a narrow window of development in the immediate perinatal period without affecting neuronal survival. Overexpressing a LIGHT mutant that selectively activates HVEM, but not one that selectively activates LTβR, also inhibited BDNF-promoted growth, suggesting that neurite growth inhibition is mediated via HVEM. Blocking HVEM signaling by a function-blocking anti-HVEM antibody significantly enhanced neurite growth from nodose neurons grown both with and without BDNF. Likewise, neurons from LIGHT-deficient neonates exhibited significantly greater neurite growth than neurons from wild-type littermates in both the presence and absence of BDNF. LIGHT overexpression significantly inhibited NF-κB activity, while preventing LIGHT-induced NF-κB inhibition by overexpressing the p65 and p50 NF-κB subunits prevented LIGHT-mediated growth inhibition. Together, these findings show that LIGHT/HVEM signaling negatively regulates neurite growth from developing sensory neurons via NF-κB inhibition.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: development; sensory neurons; TNFα; neurite; neurotrophin; transcription factor; knock-out mice
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 26/02/2014).
Publisher: Society for Neuroscience
ISSN: 0270-6474
Date of First Compliant Deposit: 30 March 2016
Last Modified: 16 Oct 2017 14:34
URI: http://orca.cf.ac.uk/id/eprint/8831

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