Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-κB activation in muramyl dipeptide recognition
Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-κB activation in muramyl dipeptide recognition
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DOI：
10.1083/jcb.200502153
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发表时间：
2005-07-04
影响因子：
7.8
通讯作者：
Podolsky, DK
中科院分区：
文献类型：
--
作者：
Barnich, N;Aguirre, JE;Podolsky, DK
核苷酸寡聚结构域（NOD） 2作为哺乳动物细胞质病原体识别分子，其突变形式与克罗恩病（CD）有遗传联系。NOD2与caspase激活和rip样相互作用caspase样凋亡调节蛋白激酶(RICK)/RIP2的募集结构域相关，激活上皮细胞和巨噬细胞中的核因子(NF)- κ B，而NOD2突变体3020insC与CD相关，其激活NF- κ B的能力受损。为了深入了解NOD2功能的分子机制，我们对NOD2缺失和替代突变体进行了功能分析。NOD2，而不是NOD2 3020insC突变体，与肠上皮细胞的细胞膜相关。膜靶向和随后的nf - κ B激活是由NOD2 cooh末端区域的两个亮氨酸残基和一个含色氨酸的基序介导的。肠上皮细胞识别细菌muramyl二肽后，NF-kappa B激活需要NOD2的膜靶向。
Nucleotide oligomerization domain ( NOD) 2 functions as a mammalian cytosolic pathogen recognition molecule, and mutant forms have been genetically linked to Crohn's disease ( CD). NOD2 associates with the caspase activation and recruitment domain of RIP-like interacting caspase-like apoptosis regulatory protein kinase (RICK)/RIP2 and activates nuclear factor (NF)-kappa B in epithelial cells and macrophages, whereas NOD2 mutant 3020insC, which is associated with CD, shows an impaired ability to activate NF-kappa B. To gain insight into the molecular mechanisms of NOD2 function, we performed a functional analysis of deletion and substitution NOD2 mutants. NOD2, but not NOD2 3020insC mutant, associated with cell surface membranes of intestinal epithelial cells. Membrane targeting and subsequent NF-kappa B activation are mediated by two leucine residues and a tryptophan-containing motif in the COOH-terminal domain of NOD2. The membrane targeting of NOD2 is required for NF-kappa B activation after the recognition of bacterial muramyl dipeptide in intestinal epithelial cells.