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

McKelvey, Laura, Gutierrez, Humberto, Nocentini, Giuseppe , Crampton, Sean J., Davies, Alun M., 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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