FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex
FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex
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DOI：
10.1073/pnas.0908423107
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发表时间：
2010-01-12
影响因子：
11.1
通讯作者：
Umeda, Masato
中科院分区：
文献类型：
--
作者：
Ikenouchi, Junichi;Umeda, Masato
Par-3/Par-6/aPKC/Cdc42复合体调节上皮极化过程中原始粘附连接（AJs）向带状AJs的转化以及线性肌动蛋白电缆的形成。然而，这种复杂功能的机制还没有很好地阐明。在本研究中，我们发现Arf6的激活作为Par蛋白复合物的下游信号通路受到时空调节。当原始AJs形成时，Par-3招募一种支架蛋白，称为含4A的FERM结构域（FRMD4A）。FRMD4A连接par3和Arf6鸟嘌呤核苷酸交换因子（GEF），细胞分裂素-1。我们提出Par-3/FRMD4A/cytohesin-1复合体确保了Arf6的准确激活，Arf6是肌动蛋白细胞骨架动力学和膜运输的核心参与者，在连接重构和上皮极化过程中。
The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables during epithelial polarization. However, the mechanisms by which this complex functions are not well elucidated. In the present study, we found that activation of Arf6 is spatiotemporally regulated as a downstream signaling pathway of the Par protein complex. When primordial AJs are formed, Par-3 recruits a scaffolding protein, termed the FERM domain containing 4A (FRMD4A). FRMD4A connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1. We propose that the Par-3/FRMD4A/cytohesin-1 complex ensures accurate activation of Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization.