Author: ["Martijn Gloerich","Jean Paul ten Klooster","Marjolein J. Vliem","Thijs Koorman","Fried J. Zwartkruis","Hans Clevers","Johannes L. Bos"]
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Abstract
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)P2 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. Microvilli are essential for the function of intestinal cells. Bos and colleagues have found that the polarity kinase LKB-1 induces PtdIns(4,5)P2 enrichment at the apical membrane. This leads to the successive accumulation of phosphatidic acid and the small GTPase Rap2A with its GEF and its effectors. These, in turn, trigger the changes in the actin cytoskeleton responsible for microvilli formation.Cite this article
Gloerich, M., ten Klooster, J., Vliem, M. et al. Rap2A links intestinal cell polarity to brush border formation. Nat Cell Biol 14, 793–801 (2012). https://doi.org/10.1038/ncb2537 