title: The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling.
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.
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork ,  Cork ,  Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: McKelvey
authors.forename: Humberto
authors.initials: H
authors.lastname: Gutierrez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nocentini
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Crampton
authors.forename: Alun M
authors.initials: AM
authors.lastname: Davies
authors.forename: Carlo R
authors.initials: CR
authors.lastname: Riccardi
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'keeffe