CD95L concatemers highlight difference in the manner CD95-mediated apoptotic and non-apoptotic pathways are triggered

Abstract

AbstractTo better understand the stoichiometry of CD95L required to trigger apoptotic and non-apoptotic signals, we generated several CD95L concatemers from dimer to hexamer conjugatedviaa flexible link (GGGGS)2. These ligands reveal that although the hexameric structure is the best stoichiometry to trigger cell death, a dimer is sufficient to induce the apoptotic response in CD95-sensitive Jurkat cells. Interestingly, only trimeric and hexameric forms can implement a potent Ca2+response, suggesting that while CD95 aggregation controls the implementation of the apoptotic signal, both aggregation and conformation are required to implement the Ca2+pathway.