| First Author | Fu X | Year | 2010 |
| Journal | Mol Biol Cell | Volume | 21 |
| Issue | 1 | Pages | 36-49 |
| PubMed ID | 19864463 | Mgi Jnum | J:309828 |
| Mgi Id | MGI:6711115 | Doi | 10.1091/mbc.e09-04-0321 |
| Citation | Fu X, et al. (2010) Retrograde neurotrophic signaling requires a protein interacting with receptor tyrosine kinases via C2H2 zinc fingers. Mol Biol Cell 21(1):36-49 |
| abstractText | Neurotrophins at axonal terminals signal to cell bodies to regulate neuronal development via signaling endosomes containing activated Trk receptor tyrosine kinases and mitogen-activated protein kinases (MAPKs). Requirements for the formation of signaling endosomes remain, however, poorly characterized. Here we show that a novel Trk-interacting protein, NTRAP (neurotrophic factor receptor-associated protein), plays a crucial role in this signaling process. NTRAP interacts with the Trk intracellular domain through its C(2)H(2) zinc fingers in a kinase-dependent manner. It is associated with vesicles, some of which contain markers for signaling endosomes. Inhibition of NTRAP function suppresses neurotrophin-induced neurite outgrowth in PC12 cells by altering TrkA endocytic traffic, inhibiting the formation of endosomes containing persistently active MAPKs. In compartmentalized sensory neuron cultures, down-regulation of NTRAP abolishes the ability of neurotrophins applied to distal axons to activate the transcription factor adenosine 3',5'-monophosphate response element-binding protein (CREB) and to promote neuronal survival. We propose that NTRAP regulates retrograde neurotrophic signaling by controlling the formation of signaling endosomes. |
