The long form of fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis
Segura Ginard, Miguel Francisco
Solé Serra, Carme
Moubarak, Rana S.
Pérez García, María José
Iglesias Guimarais, Victoria
Bayascas Ramírez, José Ramón
Llecha Cano, Núria
Rodríguez Álvarez, José
Yuste Mateos, Víctor J. (Víctor José)
Comella i Carnicé, Joan Xavier
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Death receptors (DRs) and their ligands are expressed in developing nervous system. However, neurons are generally resistant to death induction through DRs and rather their activation promotes neuronal outgrowth and branching. These results suppose the existence of DRs antagonists expressed in the nervous
system. Fas apoptosis inhibitory molecule (FAIMS ) was first identified as a Fas antagonist in B-cells. Soon after, a longer alternative spliced isoform with unknown function was identified and named FAIML. FAIMS is widely expressed, including the nervous system, and we have shown previously that it promotes neuronal differentiation but it is not an anti-apoptotic molecule in this system. Here, we demonstrate that FAIML is expressed specifically in neurons, and its expression is regulated during the development. Expression could be induced by NGF through the extracellular regulated kinase pathway in PC12(pheochromocytoma cell line) cells. Contrary to FAIMS , FAIML does not increase the neurite outgrowth induced by neurotrophins and does not interfere with nuclear factor ĸB pathway activation as FAIMS does. Cells overexpressing FAIML are resistant to apoptotic cell death induced by DRs such as Fas or tumor necrosis factor R1. Reduction of endogenous expression by small interfering RNA shows that endogenousFAIML protects primary neurons from DR-induced cell death. The detailed analysis of this antagonism shows thatFAIML can bind to Fas receptor and prevent the activation of the initiator caspase-8 induced by Fas. In conclusion, our results indicate that FAIML could be responsible for maintaining initiator caspases inactive after receptor engagement protecting neurons from the cytotoxic action of death ligands.
Is part ofThe Journal of neuroscience, 2007, vol. 27, núm. 42, p. 11228-11241
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