The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kapp B signaling.
The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-kapp B signaling.
复制标题
死亡受体拮抗剂FAIM通过依赖ERK和NF-KAPP B信号传导的机制促进神经突生长。
DOI：
10.1083/jcb.200403093
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发表时间：
2004-11-08
影响因子：
7.8
通讯作者：
Comella, Joan X
中科院分区：
文献类型：
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作者：
Sole, Carme;Dolcet, Xavier;Segura, Miguel F;Gutierrez, Humberto;Diaz-Meco, Maria-Teresa;Gozzelino, Raffaella;Sanchis, Daniel;Bayascas, Jose R;Gallego, Carme;Moscat, Jorge;Davies, Alun M;Comella, Joan X
Fas凋亡抑制分子（FAIM）是一种被鉴定为Fas诱导的细胞死亡的拮抗剂的蛋白质。我们发现，FAIM过表达未能拯救神经元从营养因子剥夺，但在不同的神经元系统中发挥显着的轴突生长促进作用。而FAIM过表达大大增强了从PC 12细胞和与神经生长因子（NGF）一起生长的交感神经元的神经突生长，通过RNAi降低内源性FAIM水平降低了这些细胞中的神经突生长。FAIM过表达促进NF-κB激活，通过使用超阻遏物IκBα或通过使用缺乏p65 NF-κB亚基的小鼠皮质神经元进行实验来阻断这种激活，可以防止FAIM诱导的神经突生长。FAIM对神经突生长的影响也通过抑制Ras-ERK途径而被阻断。最后，我们发现FAIM与Trk和p75神经营养因子受体NGF受体以配体依赖性方式相互作用。这些结果揭示了FAIM通过激活Ras-ERK通路和NF-κB促进神经突起生长的新功能。
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-κB activation, and blocking this activation by using a super-repressor IκBα or by carrying out experiments using cortical neurons from mice that lack the p65 NF-κB 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-κB.