PAR-3 mediates the initial clustering and apical localization of junction and polarity proteins during C. elegans intestinal epithelial cell polarization

Development. 2010 Jun;137(11):1833-42. doi: 10.1242/dev.047647. Epub 2010 Apr 28.

Abstract

The apicobasal polarity of epithelial cells is critical for organ morphogenesis and function, and loss of polarity can promote tumorigenesis. Most epithelial cells form when precursor cells receive a polarization cue, develop distinct apical and basolateral domains and assemble junctions near their apical surface. The scaffolding protein PAR-3 regulates epithelial cell polarity, but its cellular role in the transition from precursor cell to polarized epithelial cell has not been determined in vivo. Here, we use a targeted protein-degradation strategy to remove PAR-3 from C. elegans embryos and examine its cellular role as intestinal precursor cells become polarized epithelial cells. At initial stages of polarization, PAR-3 accumulates in cortical foci that contain E-cadherin, other adherens junction proteins, and the polarity proteins PAR-6 and PKC-3. Using live imaging, we show that PAR-3 foci move apically and cluster, and that PAR-3 is required to assemble E-cadherin into foci and for foci to accumulate at the apical surface. We propose that PAR-3 facilitates polarization by promoting the initial clustering of junction and polarity proteins that then travel and accumulate apically. Unexpectedly, superficial epidermal cells form apical junctions in the absence of PAR-3, and we show that PAR-6 has a PAR-3-independent role in these cells to promote apical junction maturation. These findings indicate that PAR-3 and PAR-6 function sequentially to position and mature apical junctions, and that the requirement for PAR-3 can vary in different types of epithelial cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cadherins / metabolism
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Polarity / physiology*
  • DNA, Helminth / genetics
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Intercellular Junctions / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Intestines / embryology
  • Molecular Sequence Data
  • Mutation
  • Protein Serine-Threonine Kinases
  • RNA Interference

Substances

  • Cadherins
  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • par-6 protein, C elegans
  • PAR-3 protein, C elegans
  • Protein Serine-Threonine Kinases