Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces.
Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces.
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DOI：
10.1016/j.chom.2021.12.011
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发表时间：
2022-02-09
影响因子：
30.3
通讯作者：
Lencer WI
中科院分区：
文献类型：
--
作者：
Maeda K;Zachos NC;Orzalli MH;Schmieder SS;Chang D;Bugda Gwilt K;Doucet M;Baetz NW;Lee S;Crawford SE;Estes MK;Kagan JC;Turner JR;Lencer WI
极化的上皮细胞在粘膜表面形成抵抗感染的基本屏障。许多病原体通常通过选择细胞内吞机制通过内腔（顶端）细胞表面进入细胞而突破这一屏障引起疾病。我们最近发现，细胞极性基因PARD 6 B的丧失选择性地减少顶端内体功能。在这里，我们发现，在响应上皮细胞进入某些病毒和细菌毒素通过顶端膜，PARD 6 B和aPKC，PARD 6 B-aPKC-Cdc 42顶端极性复合物的两个组件进行快速蛋白酶体依赖性降解。毒素或病毒结合信号对顶膜鞘糖脂的扰动，诱导PARD 6 B降解。PARD 6 B的缺失导致顶端内体功能的耗尽，并使细胞对来自内腔细胞表面的进一步感染具有抗性-从而实现一种形式的细胞自主宿主防御。Maeda et.等人发现肠上皮细胞感知霍乱毒素和轮状病毒的顶端膜结合以诱导PARD 6 B/aPKC复合物的蛋白酶体依赖性降解。这导致顶端内体的下调，其阻断进一步感染，代表细胞自主宿主防御的一种形式。
Polarized epithelial cells form the essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to epithelial cell entry of certain viruses and bacterial toxins via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex undergo rapid proteasome-dependent degradation. Perturbation of apical membrane glycosphingolipids by toxin or virus binding signals to induce the degradation of PARD6B. The loss of PARD6B causes depletion of apical endosome function and renders the cell resistant to further infection from the lumenal cell surface - thus enabling a form of cell-autonomous host defense. Maeda et. al. discover that intestinal epithelial cells sense the apical membrane binding of cholera toxin and rotavirus to induce proteasome-dependent degradation of the PARD6B/aPKC complex. This leads to down regulation of the apical endosome which blocks further infection, representing a form of cell autonomous host defense.
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