| First Author | Ichim G | Year | 2013 |
| Journal | Mol Cell | Volume | 51 |
| Issue | 5 | Pages | 632-46 |
| PubMed ID | 24034695 | Mgi Jnum | J:205925 |
| Mgi Id | MGI:5547437 | Doi | 10.1016/j.molcel.2013.08.021 |
| Citation | Ichim G, et al. (2013) The dependence receptor TrkC triggers mitochondria-dependent apoptosis upon Cobra-1 recruitment. Mol Cell 51(5):632-46 |
| abstractText | The neurotrophin receptor TrkC was recently identified as a dependence receptor, and, as such, it triggers apoptosis in the absence of its ligand, NT-3. The molecular mechanism for apoptotic engagement involves the double cleavage of the receptor's intracellular domain, leading to the formation of a proapoptotic "killer" fragment (TrkC KF). Here, we show that TrkC KF interacts with Cobra1, a putative cofactor of BRCA1, and that Cobra1 is required for TrkC-induced apoptosis. We also show that, in the developing chick neural tube, NT-3 silencing is associated with neuroepithelial cell death that is rescued by Cobra1 silencing. Cobra1 shuttles TrkC KF to the mitochondria, where it promotes Bax activation, cytochrome c release, and apoptosome-dependent apoptosis. Thus, we propose that, in the absence of NT-3, the proteolytic cleavage of TrkC leads to the release of a killer fragment that triggers mitochondria-dependent apoptosis via the recruitment of Cobra1. |
