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首页> 外文期刊>Molecular and Cellular Biology >Induction of the Alternative NF-κB Pathway by Lymphotoxin αβ (LTαβ) Relies on Internalization of LTβ Receptor
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Induction of the Alternative NF-κB Pathway by Lymphotoxin αβ (LTαβ) Relies on Internalization of LTβ Receptor

机译：淋巴毒素αβ（LTαβ）诱导替代性NF-κB途径依赖于LTβ受体的内在化

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Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB.
机译：几个肿瘤坏死因子受体（TNFR）家族成员激活经典和替代的NF-κB途径。但是，单个受体如何参与这两个不同的途径仍然知之甚少。使用淋巴毒素β受体（LTβR）作为原型，我们显示了替代途径（而非传统的NF-κB途径）的激活依赖于受体的内在化。进一步的分子分析显示了LTβR的特定胞质区，这对于其内在化，TRAF3募集和p100加工至关重要。有趣的是，我们发现LTβR的依赖于动力的，但不依赖网格蛋白的内在化似乎是激活替代途径（而不是经典的NF-κB途径）所必需的。 体内，配体诱导的肠系膜淋巴结基质细胞中LTβR的内在化与其他NF-κB靶基因的诱导有关。因此，我们的数据阐明了LTβR细胞运输是NF-κB特定生物学功能所需的过程。

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