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多 PDZ 域蛋白-1(MUPP-1)的表达调节 PALS-1/PATJ 极性复合物的细胞水平。

The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex.

机构信息

Aix-Marseille Université, CNRS, IBDM UMR7288, 13288 Marseille, France.

出版信息

Exp Cell Res. 2013 Oct 15;319(17):2514-25. doi: 10.1016/j.yexcr.2013.07.011. Epub 2013 Jul 20.

Abstract

MUPP-1 (multi-PDZ domain protein-1) and PATJ (PALS-1-associated tight junction protein) proteins are closely related scaffold proteins and bind to many common interactors including PALS-1 (protein associated with Lin seven) a member of the Crumbs complex. Our goal is to understand how MUPP-1 and PATJ and their interaction with PALS-1 are regulated in the same cells. We have shown that in MCF10A cells there are at least two different and co-existing complexes, PALS-1/MUPP-1 and PALS-1/PATJ. Surprisingly, MUPP-1 levels inversely correlated with PATJ protein levels by acting on the stabilization of the PATJ/PALS-1 complex. Upon MUPP-1 depletion, the increased amounts of PATJ are in part localized at the migrating front of MCF10A cells and are able to recruit more PAR3 (partition defective 3). All together these data indicate that a precise balance between MUPP-1 and PATJ is achieved in epithelial cells by regulating their association with PALS-1.

摘要

MUPP-1(多 PDZ 结构域蛋白-1)和 PATJ(PALS-1 相关紧密连接蛋白)蛋白是密切相关的支架蛋白,与许多共同的相互作用因子结合,包括 PALS-1(与 Lin7 相关的蛋白),它是 Crumbs 复合物的一个成员。我们的目标是了解 MUPP-1 和 PATJ 及其与 PALS-1 的相互作用如何在相同的细胞中被调控。我们已经表明,在 MCF10A 细胞中,至少存在两种不同且共存的复合物,即 PALS-1/MUPP-1 和 PALS-1/PATJ。令人惊讶的是,MUPP-1 通过作用于 PATJ/PALS-1 复合物的稳定性,与 PATJ 蛋白水平呈负相关。在 MUPP-1 耗竭后,PATJ 的增加量部分定位于 MCF10A 细胞的迁移前沿,并且能够募集更多的 PAR3(partition defective 3)。所有这些数据表明,在上皮细胞中,通过调节它们与 PALS-1 的结合,MUPP-1 和 PATJ 之间达到了精确的平衡。

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