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

The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex
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DOI:
10.1016/j.yexcr.2013.07.011
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发表时间:
2013-10-15
影响因子:
3.7
通讯作者:
Massey-Harroche, Dominique
Massey-Harroche, Dominique
中科院分区:
医学3区
文献类型:
--
作者:
Assemat, Emeline;Crost, Emmanuelle;Massey-Harroche, Dominique

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MUPP-1(多PDZ结构域蛋白-I)和PATJ(PALS-1相关紧密连接蛋白)是密切相关的支架蛋白,并与许多常见的相互作用蛋白结合,其中PALS-1(与LIN7相关的蛋白)是Crumbs复合体的成员。我们的目标是了解MUPP-1和PATJ以及它们与PALS-1的相互作用是如何在同一细胞中调节的。我们已经证明在MCF10A细胞中至少存在两种不同的共存的复合体,PALS-1/MUPP-1和PALS-1/PATJ。令人惊讶的是,Mupp-1水平与PATJ蛋白水平呈负相关,这是通过作用于PATJ/PALS-1复合体的稳定而实现的。当MUPP-1耗尽时,增加的PATJ部分定位于MCF10A细胞的迁移前沿,并能够招募更多的PAR3(分区缺陷3)。所有这些数据表明,通过调节MUPP-1和PATJ与PALS-1的联系,在上皮细胞中实现了MUPP-1和PATJ之间的精确平衡。(C)2013 Elsevier Inc.保留所有权利。
MUPP-1 (multi-PDZ domain protein-I) 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. (C) 2013 Elsevier Inc. All rights reserved.