Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.
Nat Cell Biol. 2012 Aug;14(8):793-801. doi: 10.1038/ncb2537. Epub 2012 Jul 15.
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.
在高度极化的肠上皮细胞的顶端，微绒毛刷状缘允许从肠腔中调节吸收营养物质。在这里，我们确定小 G 蛋白 Rap2A 作为一个分子链接，将微绒毛的形成直接与前面的细胞极化联系起来。顶端基底极性的建立可以被单个分离的结肠细胞中的激酶 LKB1 触发，导致 PtdIns(4,5)P(2)在顶端膜上的富集。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、其效应物 TNIK、激酶 MST4 以及最终的肌动蛋白结合蛋白 Ezrin 的连续信号提供了局部线索。因此，上皮细胞极化通过一个小 G 蛋白信号模块直接转化为刷状缘的获得，该模块的作用由皮质脂质线索定位。
