RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer.
RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer.
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DOI：
10.1016/j.biocel.2015.02.020
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Terry SJ
中科院分区：
文献类型：
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作者：
Zihni C;Terry SJ
为了正常发育和体内平衡，必须正确控制上皮极性的建立和维持。脊椎动物中的紧密连接 (TJ) 通过 TJ 本身和与其相关的细胞骨架之间的双向、复杂的信号通路定义了极化上皮细胞的顶端和基底外侧膜域。 RhoGTP 酶是这些过程的核心，有证据表明它们的调节是通过 GEF 和 GAP 与连接的细胞质接头蛋白之间的相互作用来协调的。在这篇 InFocus 综述中，我们确定这些接头蛋白的表达、定位或稳定性在各种癌症中发生了改变，可能代表极性丧失与癌症之间的重要机制联系。我们在这里重点关注两种已充分表征的 RhoGTPases Cdc42 和 RhoA，它们的 GEF 和 GAP 主要通过细胞质接头蛋白定位于 TJ。
The establishment and maintenance of epithelial polarity must be correctly controlled for normal development and homeostasis. Tight junctions (TJ) in vertebrates define apical and basolateral membrane domains in polarized epithelia via bi-directional, complex signalling pathways between TJ themselves and the cytoskeleton they are associated with. RhoGTPases are central to these processes and evidence suggests that their regulation is coordinated by interactions between GEFs and GAPs with junctional, cytoplasmic adapter proteins. In this InFocus review we determine that the expression, localization or stability of a variety of these adaptor proteins is altered in various cancers, potentially representing an important mechanistic link between loss of polarity and cancer. We focus here, on two well characterized RhoGTPases Cdc42 and RhoA who's GEFs and GAPs are predominantly localized to TJ via cytoplasmic adaptor proteins.