| First Author | McKelvey L | Year | 2012 |
| Journal | Biol Open | Volume | 1 |
| Issue | 10 | Pages | 1016-23 |
| PubMed ID | 23213379 | Mgi Jnum | J:187955 |
| Mgi Id | MGI:5438826 | Doi | 10.1242/bio.20121024 |
| Citation | McKelvey L, et al. (2012) The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-kappaB signalling. Biol Open 1(10):1016-1023 |
| abstractText | NF-kappaB 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-kappaB to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-kappaB 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-kappaB activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-kappaB 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-kappaB signalling, which provides an optimal environment for NGF-promoted growth. |
