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

ABSTRACT: NF-?B 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-?B to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-?B 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-?B activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-?B 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-?B signalling, which provides an optimal environment for NGF-promoted growth.

SUBMITTER: McKelvey L 

PROVIDER: S-EPMC3507174 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature