Fucosylated glycoproteins and fucosylated glycolipids play opposing roles in cholera intoxication.
Fucosylated glycoproteins and fucosylated glycolipids play opposing roles in cholera intoxication.
复制标题
岩藻糖基化糖蛋白和岩藻糖基化糖脂在霍乱中毒中发挥相反的作用。
DOI：
10.1101/2023.08.02.551727
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kohler,JenniferJ
中科院分区：
文献类型：
--
作者：
Ghorashi,AtossaC;Boucher,Andrew;Archer-Hartmann,StephanieA;Murray,NathanB;Konada,RohitSaiReddy;Zhang,Xunzhi;Xing,Chao;Azadi,Parastoo;Yrlid,Ulf;Kohler,JenniferJ
霍乱毒素(CT)是霍乱的病原体。在此，我们报道了多种岩藻糖化糖结合物在CT结合和肠上皮细胞中毒中的作用。在Colo205细胞中，B3GNT5的敲除减少了CT的结合，但使细胞对中毒敏感。B3GNT5是合成乳酸和新乳酸系列糖脂(GSLS)所需的酶。过量表达B3GNT5产生更多岩藻糖化的GSLS对中毒具有保护作用，表明岩藻糖化的GSLS是CT的诱骗受体。B3GALT5基因敲除(KO)导致岩藻糖基化O-连接和N-连接糖蛋白的产生增加，并导致CT结合增加和中毒。在B3GALT5 KO细胞中敲除B3GNT5可以消除岩藻糖化GSLS的产生，但会增加中毒程度，从而确定岩藻糖化糖蛋白是CT的功能性受体。这些发现为调节宿主细胞CT敏感性的分子决定因素提供了洞察力。
Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout of B3GNT5, the enzyme required for synthesis of lacto- and neolacto-series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. Knockout (KO) of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins, and leads to increased CT binding and intoxication. Knockout of B3GNT5 in B3GALT5 KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into molecular determinants regulating CT sensitivity of host cells.