The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kapp B signaling.

TitleThe death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kapp B signaling.
Publication TypeJournal Article
Year of Publication2004
AuthorsSole C, Dolcet X, Segura MF, Gutierrez H, Diaz-Meco M-T, Gozzelino R, Sanchis D, Bayascas JR, Gallego C, Moscat J, Davies AM, Comella JX
JournalJ Cell Biol
Volume167
Issue3
Pagination479-92
Date Published2004 Nov 08
ISSN0021-9525
KeywordsAnimals, Apoptosis Regulatory Proteins, Humans, MAP Kinase Signaling System, Mice, Neurites, Neurons, NF-kappa B, Oncogene Proteins, PC12 Cells, Proteins, Rats, Receptor, Nerve Growth Factor, Receptors, Nerve Growth Factor, RNA, Small Interfering, Signal Transduction, Transfection
Abstract

Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist of Fas-induced cell death. We show that FAIM overexpression fails to rescue neurons from trophic factor deprivation, but exerts a marked neurite growth-promoting action in different neuronal systems. Whereas FAIM overexpression greatly enhanced neurite outgrowth from PC12 cells and sympathetic neurons grown with nerve growth factor (NGF), reduction of endogenous FAIM levels by RNAi decreased neurite outgrowth in these cells. FAIM overexpression promoted NF-kappa B activation, and blocking this activation by using a super-repressor I kappa B alpha or by carrying out experiments using cortical neurons from mice that lack the p65 NF-kappa B subunit prevented FAIM-induced neurite outgrowth. The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras-ERK pathway. Finally, we show that FAIM interacts with both Trk and p75 neurotrophin receptor NGF receptors in a ligand-dependent manner. These results reveal a new function of FAIM in promoting neurite outgrowth by a mechanism involving activation of the Ras-ERK pathway and NF-kappa B.

DOI10.1083/jcb.200403093
Alternate JournalJ Cell Biol
PubMed ID15520226
PubMed Central IDPMC2172486
Grant List / / Wellcome Trust / United Kingdom
071251 / / Wellcome Trust / United Kingdom
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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