title: PAR-3 mediates the initial clustering and apical localization of junction and polarity proteins during C. elegans intestinal epithelial cell polarization.
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.
authors.affiliation: Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Annita
authors.initials: A
authors.lastname: Achilleos
authors.forename: Ann M
authors.initials: AM
authors.lastname: Wehman
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nance
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D018509:DNA, Helminth / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D007365:Intercellular Junctions / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000196:embryology; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; C512642:par-6 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases