A molecular network for de novo generation of the apical surface and lumen

Nat Cell Biol. 2010 Nov;12(11):1035-45. doi: 10.1038/ncb2106. Epub 2010 Oct 3.

Abstract

To form epithelial organs cells must polarize and generate de novo an apical domain and lumen. Epithelial polarization is regulated by polarity complexes that are hypothesized to direct downstream events, such as polarized membrane traffic, although this interconnection is not well understood. We have found that Rab11a regulates apical traffic and lumen formation through the Rab guanine nucleotide exchange factor (GEF), Rabin8, and its target, Rab8a. Rab8a and Rab11a function through the exocyst to target Par3 to the apical surface, and control apical Cdc42 activation through the Cdc42 GEF, Tuba. These components assemble at a transient apical membrane initiation site to form the lumen. This Rab11a-directed network directs Cdc42-dependent apical exocytosis during lumen formation, revealing an interaction between the machineries of vesicular transport and polarization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Annexin A2 / metabolism
  • Cell Membrane / metabolism
  • Cell Polarity / physiology*
  • Dogs
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Germinal Center Kinases
  • Models, Biological
  • Morphogenesis*
  • Protein-Serine-Threonine Kinases / metabolism
  • cdc42 GTP-Binding Protein / metabolism
  • rab GTP-Binding Proteins / metabolism

Substances

  • Annexin A2
  • Germinal Center Kinases
  • Protein-Serine-Threonine Kinases
  • rab11 protein
  • cdc42 GTP-Binding Protein
  • rab GTP-Binding Proteins