The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling

McKelvey, Laura and Gutierrez, Humberto and Nocentini, Giuseppe and Crampton, Sean J. and Davies, Alun M. and Riccardi, Carlo R. and O'keeffe, Gerard W. (2012) The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling. Biology Open, 1 (10). pp. 1016-1023. ISSN 2046-6390

Full content URL: http://dx.doi.org/10.1242/bio.20121024

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Item Type:Article
Item Status:Live Archive

Abstract

NF-κB transcription factors play a key role in regulating the growth of neural processes in the developing PNS. Although several secreted proteins have been shown to activate NF-κB to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-κB activity present in these neurons is restricted to allow neurite growth to occur during their normal development. Here we show that activation of the glucocorticoid-induced tumour necrosis factor receptor (GITR) inhibits NF-κB activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-κB dependent gene transcription and a decrease in Erk activation leading to a reduction in neurite growth. These findings show that GITR signalling can regulate the extent of sympathetic neurite growth through an inverse modulation of Erk and NF-κB signalling, which provides an optimal environment for NGF-promoted growth.

Keywords:Neuronal Development
Subjects:C Biological Sciences > C141 Developmental Biology
Divisions:College of Science > School of Life Sciences
ID Code:7850
Deposited On:21 Mar 2013 16:11

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