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

Sole C, Dolcet X, Segura MF, Gutierrez H, Diaz-Meco MT, Gozzelino R, Sanchis D, Bayascas JR, Gallego C, Moscat J, Davies AM, Comella JX - J. Cell Biol. (2004)

Bottom Line: 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.The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras-ERK pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Group Cell Signalling and Apoptosis, Department of Basic Medical Sciences, Universitat de Lleida, 25008 Lleida, Spain.

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.

Show MeSH

Related in: MedlinePlus

FAIM-induced increase in neurite outgrowth is eliminated in cortical neurons from p65−/− mouse embryos. Cultured cortical neurons from p65+/+ (WT) or p65−/− (KO) mice were transfected with eYFP alone or with eYFP plus FAIM-S. After 24 h, labeled cortical neurons were visualized, digitally acquired, and measured. (A) Drawings of neurons that represent the 25, 50, 75, and 100 percentiles of neurite length measurements. (B) Micrograph showing representative cells of p65+/+ (WT) or p65−/− genotypes (KO) transfected with the indicated plasmids. (C) Quantification of the neurite outgrowth performed by tracing the neuritic arbors and measuring the neuritic length (top) and branching points (bottom). Bars, 50 μm. *, P < 0.001; t test.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172486&req=5

fig8: FAIM-induced increase in neurite outgrowth is eliminated in cortical neurons from p65−/− mouse embryos. Cultured cortical neurons from p65+/+ (WT) or p65−/− (KO) mice were transfected with eYFP alone or with eYFP plus FAIM-S. After 24 h, labeled cortical neurons were visualized, digitally acquired, and measured. (A) Drawings of neurons that represent the 25, 50, 75, and 100 percentiles of neurite length measurements. (B) Micrograph showing representative cells of p65+/+ (WT) or p65−/− genotypes (KO) transfected with the indicated plasmids. (C) Quantification of the neurite outgrowth performed by tracing the neuritic arbors and measuring the neuritic length (top) and branching points (bottom). Bars, 50 μm. *, P < 0.001; t test.

Mentions: To further confirm the role of NF-κB in mediating FAIM-induced neurite outgrowth, we compared the neurite arbors in cultures established from wild-type embryos and embryos with a mutation of the p65 gene (Beg et al., 1995). We used primary cultures of cortical neurons instead of SCG neurons for these studies because the latest stage at which these experiments could be performed was at day 15 of gestation (E15), since p65−/− embryos die in utero shortly after this stage. After 3-h culture, E15 cortical neurons were ballistically transfected with gold particles coated with FAIM plus eYFP or pcDNA3 plus eYFP, and neurite arbors were analyzed after a further 24-h incubation. Fig. 8 shows that p65+/+ cortical neurons overexpressing FAIM had more extensive (50–60% longer) and more branched neurite arbors (80–120% more branch points) than control transfected neurons. This increase in neurite growth and complexity between FAIM-transfected and control-transfected neurons was not observed in cultures established from p65−/− littermates. These results additionally indicate that a functional NF-κB is required for FAIM-induced neurite outgrowth in cortical neurons.


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

Sole C, Dolcet X, Segura MF, Gutierrez H, Diaz-Meco MT, Gozzelino R, Sanchis D, Bayascas JR, Gallego C, Moscat J, Davies AM, Comella JX - J. Cell Biol. (2004)

FAIM-induced increase in neurite outgrowth is eliminated in cortical neurons from p65−/− mouse embryos. Cultured cortical neurons from p65+/+ (WT) or p65−/− (KO) mice were transfected with eYFP alone or with eYFP plus FAIM-S. After 24 h, labeled cortical neurons were visualized, digitally acquired, and measured. (A) Drawings of neurons that represent the 25, 50, 75, and 100 percentiles of neurite length measurements. (B) Micrograph showing representative cells of p65+/+ (WT) or p65−/− genotypes (KO) transfected with the indicated plasmids. (C) Quantification of the neurite outgrowth performed by tracing the neuritic arbors and measuring the neuritic length (top) and branching points (bottom). Bars, 50 μm. *, P < 0.001; t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172486&req=5

fig8: FAIM-induced increase in neurite outgrowth is eliminated in cortical neurons from p65−/− mouse embryos. Cultured cortical neurons from p65+/+ (WT) or p65−/− (KO) mice were transfected with eYFP alone or with eYFP plus FAIM-S. After 24 h, labeled cortical neurons were visualized, digitally acquired, and measured. (A) Drawings of neurons that represent the 25, 50, 75, and 100 percentiles of neurite length measurements. (B) Micrograph showing representative cells of p65+/+ (WT) or p65−/− genotypes (KO) transfected with the indicated plasmids. (C) Quantification of the neurite outgrowth performed by tracing the neuritic arbors and measuring the neuritic length (top) and branching points (bottom). Bars, 50 μm. *, P < 0.001; t test.
Mentions: To further confirm the role of NF-κB in mediating FAIM-induced neurite outgrowth, we compared the neurite arbors in cultures established from wild-type embryos and embryos with a mutation of the p65 gene (Beg et al., 1995). We used primary cultures of cortical neurons instead of SCG neurons for these studies because the latest stage at which these experiments could be performed was at day 15 of gestation (E15), since p65−/− embryos die in utero shortly after this stage. After 3-h culture, E15 cortical neurons were ballistically transfected with gold particles coated with FAIM plus eYFP or pcDNA3 plus eYFP, and neurite arbors were analyzed after a further 24-h incubation. Fig. 8 shows that p65+/+ cortical neurons overexpressing FAIM had more extensive (50–60% longer) and more branched neurite arbors (80–120% more branch points) than control transfected neurons. This increase in neurite growth and complexity between FAIM-transfected and control-transfected neurons was not observed in cultures established from p65−/− littermates. These results additionally indicate that a functional NF-κB is required for FAIM-induced neurite outgrowth in cortical neurons.

Bottom Line: 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.The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras-ERK pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Group Cell Signalling and Apoptosis, Department of Basic Medical Sciences, Universitat de Lleida, 25008 Lleida, Spain.

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.

Show MeSH
Related in: MedlinePlus