Development and application of chemical proteomics identify p120-catenin glutathionylation regulating E-cadherin stability. Kukulage et al.

One important function of p120 is to bind and stabilize E-cadherin at the plasma membrane. Therefore, we examined the localization of p120 and E-cadherin in high and low glucose conditions. In MCF7 cells expressing p120 WT, E-cadherin was mainly localized at the membrane. p120 (FLAG, red) showed high co-localization with E-cadherin (green) under high glucose (25 mM) (Pearson coefficient 0.69 ± 0.09, n = 35). On the other hand, under low glucose (5 mM), p120 was distributed to the cytoplasm, whereas E-cadherin was mainly localized to the membrane, significantly decreasing their co-localization (Pearson coefficient 0.34 ± 0.06, n = 35). Importantly, MCF7 cells expressing p120 C692S showed high co-localization of p120 and E-cadherin in high glucose (25 mM) (Pearson coefficient 0.71 ± 0.09, n = 35), and the co-localization remained relatively unchanged even in low glucose (5 mM) (Pearson coefficient 0.68 ± 0.09, n = 35), supporting that p120 C692 glutathionylation (or oxidation) is responsible for the cytoplasmic redistribution of p120 under the stressed condition.

p120蛋白在维持细胞骨架结构中扮演着至关重要的角色，其一项重要功能是于质膜上结合并稳定E-钙粘蛋白。鉴于此，本研究对p120与E-钙粘蛋白在高糖与低糖条件下的定位进行了探讨。在表达野生型p120的MCF7细胞中，E-钙粘蛋白主要定位于细胞膜。在高糖（25 mM）条件下，p120（标记为FLAG，红色）与E-钙粘蛋白（绿色）呈现出高程度的共定位（皮尔逊相关系数为0.69 ± 0.09，样本量n = 35）。反之，在低糖（5 mM）条件下，p120蛋白分布至细胞质中，而E-钙粘蛋白则主要定位于细胞膜，两者共定位程度显著下降（皮尔逊相关系数为0.34 ± 0.06，样本量n = 35）。值得注意的是，在表达p120 C692S的MCF7细胞中，p120与E-钙粘蛋白在高糖（25 mM）条件下展现出高程度的共定位（皮尔逊相关系数为0.71 ± 0.09，样本量n = 35），且即便在低糖（5 mM）条件下，共定位程度亦保持相对稳定（皮尔逊相关系数为0.68 ± 0.09，样本量n = 35），此结果支持了p120 C692位点的谷胱甘肽化（或氧化）是导致p120在应激条件下细胞质重新分布的成因。