Rap2A links intestinal cell polarity to brush border formation.
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.
Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.
Martijn
M
Gloerich
Jean Paul
JP
ten Klooster
Marjolein J
MJ
Vliem
Thijs
T
Koorman
Fried J
FJ
Zwartkruis
Hans
H
Clevers
Johannes L
JL
Bos
D000818:Animals; D018938:Caco-2 Cells; D017173:Caenorhabditis elegans; D002460:Cell Line; D016764:Cell Polarity; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000081410:Germinal Center Kinases; D057809:HEK293 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D008871:Microvilli; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020668:rap GTP-Binding Proteins / Q000378:metabolism*; D000099149:Ezrin; D000099317:Hippo Kinases
D003598:Cytoskeletal Proteins; D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases; D020668:rap GTP-Binding Proteins; D000099149:Ezrin; C430908:STK26 protein, human; D000099317:Hippo Kinases; C000631454:TNIK protein, human; C116756:RAP2A protein, human