The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling
| Autor: | Laura McKelvey, Humberto Gutierrez, Giuseppe Nocentini, Sean J. Crampton, Alun M. Davies, Carlo R. Riccardi, Gerard W. O’keeffe |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Biology Open, Vol 1, Iss 10, Pp 1016-1023 (2012) |
| Druh dokumentu: | article |
| ISSN: | 2046-6390 20121024 |
| DOI: | 10.1242/bio.20121024 |
| Popis: | Summary 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. |
| Databáze: | Directory of Open Access Journals |
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