Genetic Dissection of Neurotrophin Signaling through the p75 Neurotrophin Receptor

• DOI: 10.1016/j.celrep.2012.11.009
• Publication Date: 2012-12-20T23:16:55Z
• Authors: Ioannis Charalamp...; Annalisa Vicario; Iosif Pediaditakis; Achille Gravanis; Anastasia Simi; Carlos F. Ibáñez
• Keywords: Crosstalk; Neurite

Structural determinants underlying signaling specificity in the tumor necrosis factor receptor superfamily (TNFRSF) are poorly characterized, and it is unclear whether different outputs can be genetically dissociated. The p75 neurotrophin (p75(NTR)), also known as TNFRSF16, a key regulator of trophic injury responses nervous system. Here, we describe genetic approach for dissecting p75(NTR) deciphering its logic. important regulation cell death, NF-κB, RhoA pathways were identified death domain (DD). Proapoptotic prosurvival mapped onto nonoverlapping epitopes, demonstrating that separated p75(NTR). Dissociation c-Jun kinase (JNK) caspase-3 activities indicated JNK necessary but not sufficient p75(NTR)-mediated death. RIP2 recruitment RhoGDI release mechanistically linked, indicating competition DD binding underlies crosstalk between NF-κB signaling. These results provide insights into logic pave way dissection function physiology.