Rap2A links intestinal cell polarity to brush border formation
Rap2A links intestinal cell polarity to brush border formation
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DOI：
10.1038/ncb2537
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发表时间：
2012-08-01
影响因子：
21.3
通讯作者：
Bos, Johannes L.
中科院分区：
文献类型：
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作者：
Gloerich, Martijn;ten Klooster, Jean Paul;Bos, Johannes L.
位于高度极化的肠细胞顶端的微绒毛刷状边缘允许从肠腔中调节营养的吸收。在这里，我们确定小G蛋白Rap2A是将微绒毛的形成直接连接到之前的细胞极化的分子链接。在单个分离的结肠细胞中，可由激酶LKB1触发的根尖基极性的建立导致PtdIns(4，5)P-2在顶膜上的浓缩。随后磷脂酶D1的募集允许磷脂酸的极化积累，这为鸟嘌呤核苷酸交换因子PDZgef、小G蛋白Rap2a、其效应器Tnik、激酶MST4以及最终的肌动蛋白结合蛋白Ezrin的连续信号传递提供了局部信号。因此，上皮细胞的极化通过一个小的G蛋白信号模块直接转化为刷状边界的获得，该模块的作用由皮质脂信号定位。
The microvillus brush border at the apex of the highly polarized enterocyte allows the regulated uptake of nutrients from the intestinal lumen. Here, we identify the small G protein Rap2A as a molecular link that couples the formation of microvilli directly to the preceding cell polarization. Establishment of apicobasal polarity, which can be triggered by the kinase LKB1 in single, isolated colon cells, results in enrichment of PtdIns(4,5)P-2 at the apical membrane. The subsequent recruitment of phospholipase D1 allows polarized accumulation of phosphatidic acid, which provides a local cue for successive signalling by the guanine nucleotide exchange factor PDZGEF, the small G protein Rap2A, its effector TNIK, the kinase MST4 and, ultimately, the actin-binding protein Ezrin. Thus, epithelial cell polarization is translated directly into the acquisition of brush borders through a small G protein signalling module whose action is positioned by a cortical lipid cue.