Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry
Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry
复制标题
DOI：
10.1038/ni.1823
复制
发表时间：
2010-01-01
影响因子：
30.5
通讯作者：
Philpott, Dana J.
中科院分区：
文献类型：
--
作者：
Travassos, Leonardo H.;Carneiro, Leticia A. M.;Philpott, Dana J.
自噬正在成为一种重要的防御机制，但宿主细胞内的传感器负责诱导自噬响应细菌感染仍然未知。在这里，我们证明了细胞内传感器Nod 1和Nod 2对于入侵细菌的自噬反应至关重要。通过不依赖于衔接子RIP 2和转录因子NF-κ B的机制，Nod 1和Nod 2在细菌进入位点将自噬蛋白ATG 16 L1募集到质膜。在克罗恩病相关NOD 2移码突变的纯合细胞中，突变体Nod 2未能将ATG 16 L1招募到质膜上，并且自噬体对入侵细菌的包裹也受到损害。我们的研究结果将Nod蛋白的细菌传感与自噬的诱导联系起来，并提供了Nod 2和ATG 16 L1之间的功能联系，这两个基因是与克罗恩病相关的两个最重要的基因。
Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappa B, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease-associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.