The dependence receptor Trkc triggers mitochondria-dependent apoptosis upon Cobra-1 recruitment

Ichim, G. et al. (2013) The dependence receptor Trkc triggers mitochondria-dependent apoptosis upon Cobra-1 recruitment. Molecular Cell, 51(5), pp. 632-646. (doi: 10.1016/j.molcel.2013.08.021)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ichim, Dr Gabriel
• Authors: Ichim, G., Genevois, A.-L., Ménard, M., Yu, L.-Y., Coelho-Aguiar, J. M., Llambi, F., Jarrosson-Wuilleme, L., Lefebvre, J., Tulasne, D., Dupin, E., Le Douarin, N., Arumäe, U., Tauszig-Delamasure, S., and Mehlen, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular Cell
• Publisher: Elsevier Inc.
• ISSN: 1097-2765
• ISSN (Online): 1097-4164