Hypoglycosylated E-cadherin promotes the assembly of tight junctions through the recruitment of PP2A to adherens junctions.
Hypoglycosylated E-cadherin promotes the assembly of tight junctions through the recruitment of PP2A to adherens junctions.
复制标题
DOI：
10.1016/j.yexcr.2010.02.008
复制
发表时间：
2010-07-01
影响因子：
3.7
通讯作者：
Kukuruzinska MA
中科院分区：
文献类型：
--
作者：
Nita-Lazar M;Rebustini I;Walker J;Kukuruzinska MA
上皮细胞-细胞粘附由多蛋白复合物控制，包括E-钙粘蛋白介导的粘附连接（AJs）和含ZO-1的紧密连接（TJ）。以前，我们报告说，减少E-钙粘蛋白N-糖基化在正常和癌细胞促进稳定的AJs通过改变E-钙粘蛋白支架的组成和细胞骨架协会。在这里，我们表明，低糖基化的E-钙粘蛋白，含有AJs与蛋白磷酸酶2A（PP 2A）的相互作用增强代表了促进TJ组装的机制。在MDCK细胞中，用siRNA减弱N-糖基化途径中的第一个基因DPAGT 1的细胞N-糖基化，减少了表面E-钙粘蛋白的N-糖基化，并导致稳定蛋白γ-连环蛋白、α-连环蛋白、黏着斑蛋白和PP 2A向AJs的募集增加。PP 2A与AJs的更大关联与PP 2A与ZO-1和claudin-1的结合减少以及丝氨酸磷酸化ZO-1和claudin-1的池增加相关。在与闭合蛋白和密蛋白-1的复合物中发现更多的ZO-1，这对应于增强的跨上皮电阻（TER），表明TJ的生理组装。用低糖基化的E-钙粘蛋白变体V13转染MDCK细胞后，检测到AJs和TJ的类似成熟。我们的数据表明，E-钙粘蛋白N-聚糖协调的成熟AJs与TJ的组装，通过影响PP 2A与这些连接复合物的协会。
Epithelial cell-cell adhesion is controlled by multiprotein complexes that include E-cadherin-mediated adherens junctions (AJs) and ZO-1-containing tight junctions (TJs). Previously, we reported that reduction of E-cadherin N-glycosylation in normal and cancer cells promoted stabilization of AJs through changes in the composition and cytoskeletal association of E-cadherin scaffolds. Here, we show that enhanced interaction of hypoglycosylated E-cadherin-containing AJs with protein phosphatase 2A (PP2A) represents a mechanism for promoting TJ assembly. In MDCK cells, attenuation of cellular N-glycosylation with siRNA to DPAGT1, the first gene in the N-glycosylation pathway, reduced N-glycosylation of surface E-cadherin and resulted in increased recruitment of stabilizing proteins γ-catenin, α-catenin, vinculin and PP2A to AJs. Greater association of PP2A with AJs correlated with diminished binding of PP2A to ZO-1 and claudin-1 and with increased pools of serine-phosphorylated ZO-1 and claudin-1. More ZO-1 was found in complexes with occludin and claudin-1, and this corresponded to enhanced transepithelial resistance (TER), indicating physiological assembly of TJs. Similar maturation of AJs and TJs was detected after transfection of MDCK cells with the hypoglycosylated E-cadherin variant, V13. Our data indicate that E-cadherin N-glycans coordinate the maturity of AJs with the assembly of TJs by affecting the association of PP2A with these junctional complexes.
登录
查看更多内容
影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
E-钙粘蛋白参与通过 Rac1 刺激增殖。
DOI：
10.1083/jcb.200510087
发表时间：
2006-05-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Liu WF;Nelson CM;Pirone DM;Chen CS
通讯作者：
Chen CS
影响因子：
16
作者：
Janssen, MEW;Kim, E;Hanein, D
通讯作者：
Hanein, D
DOI：
10.1016/s1044-5781(06)80018-6
发表时间：
1995-01-01
期刊：
Seminars in Developmental Biology
影响因子：
--
作者：
Nathke, Inke S.;Hinck, Lindsay;Nelson, W. James
通讯作者：
Nelson, W. James
DOI：
10.1083/jcb.107.4.1575
发表时间：
1988-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gumbiner B;Stevenson B;Grimaldi A
通讯作者：
Grimaldi A