Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD

Cell. 2004 Feb 6;116(3):457-66. doi: 10.1016/s0092-8674(04)00114-x.

Abstract

The LKB1 gene encodes a serine/threonine kinase that is mutated in the Peutz-Jeghers cancer syndrome. LKB1 is homologous to the Par-4 polarity genes in C. elegans and D. melanogaster. We have previously reported the identification and characterization of an LKB1-specific adaptor protein, STRAD, which activates LKB1 and translocates it from nucleus to cytoplasm. We have now constructed intestinal epithelial cell lines in which inducible STRAD activates LKB1. Upon LKB1 activation, single cells rapidly remodel their actin cytoskeleton to form an apical brush border. The junctional proteins ZO-1 and p120 redistribute in a dotted circle peripheral to the brush border, in the absence of cell-cell contacts. Apical and basolateral markers sort to their respective membrane domains. We conclude that LKB1 can induce complete polarity in intestinal epithelial cells. In contrast to current thinking on polarization of simple epithelia, these cells can fully polarize in the absence of junctional cell-cell contacts.

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Caco-2 Cells
  • Cell Communication / genetics
  • Cell Polarity / physiology*
  • Humans
  • Intercellular Junctions / genetics
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / ultrastructure
  • Membrane Proteins / metabolism
  • Microscopy, Electron
  • Microvilli / metabolism*
  • Microvilli / ultrastructure
  • Peutz-Jeghers Syndrome / genetics
  • Peutz-Jeghers Syndrome / metabolism
  • Phosphoproteins / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Zonula Occludens-1 Protein
  • p120 GTPase Activating Protein / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Membrane Proteins
  • Phosphoproteins
  • STRAD protein, human
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • p120 GTPase Activating Protein
  • STK11 protein, human
  • Protein-Serine-Threonine Kinases