Rap2A links intestinal cell polarity to brush border formation

Nat Cell Biol. 2012 Aug;14(8):793-801. doi: 10.1038/ncb2537. Epub 2012 Jul 15.

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)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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Caenorhabditis elegans
  • Cell Line
  • Cell Polarity*
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • Germinal Center Kinases
  • HEK293 Cells
  • Humans
  • Intestinal Mucosa / cytology*
  • Microvilli
  • Protein-Serine-Threonine Kinases / metabolism
  • Real-Time Polymerase Chain Reaction
  • rap GTP-Binding Proteins / metabolism*

Substances

  • Cytoskeletal Proteins
  • Germinal Center Kinases
  • ezrin
  • MST4 protein, human
  • Protein-Serine-Threonine Kinases
  • TNIK protein, human
  • RAP2A protein, human
  • rap GTP-Binding Proteins