Document Detail


The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis.
MedLine Citation:
PMID:  17942717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (FAIM(S)) was first identified as a Fas antagonist in B-cells. Soon after, a longer alternative spliced isoform with unknown function was identified and named FAIM(L). FAIM(S) 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 FAIM(L) 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 FAIM(S), FAIM(L) does not increase the neurite outgrowth induced by neurotrophins and does not interfere with nuclear factor kappaB pathway activation as FAIM(S) does. Cells overexpressing FAIM(L) 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 endogenous FAIM(L) protects primary neurons from DR-induced cell death. The detailed analysis of this antagonism shows that FAIM(L) can bind to Fas receptor and prevent the activation of the initiator caspase-8 induced by Fas. In conclusion, our results indicate that FAIM(L) could be responsible for maintaining initiator caspases inactive after receptor engagement protecting neurons from the cytotoxic action of death ligands.
Authors:
Miguel F Segura; Carme Sole; Marta Pascual; Rana S Moubarak; M Jose Perez-Garcia; Raffaella Gozzelino; Victoria Iglesias; Nahuai Badiola; Jose R Bayascas; Nuria Llecha; Jose Rodriguez-Alvarez; Eduardo Soriano; Victor J Yuste; Joan X Comella
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  27     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-18     Completed Date:  2007-11-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11228-41     Citation Subset:  IM    
Affiliation:
Cell Signaling and Apoptosis Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida-Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics,  physiology*
Apoptosis Regulatory Proteins / biosynthesis*,  genetics*,  physiology
Cells, Cultured
Gene Expression Regulation / physiology
Genetic Variation / physiology
Humans
Inhibitor of Apoptosis Proteins / physiology*
Mice
Neurons / metabolism*,  pathology
PC12 Cells
Protein Isoforms / biosynthesis,  genetics,  physiology
Rats
Receptors, Death Domain / antagonists & inhibitors*,  genetics,  physiology*
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/FAIM protein, human; 0/Inhibitor of Apoptosis Proteins; 0/Protein Isoforms; 0/Receptors, Death Domain

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