Remodeling the zonula adherens in response to tension and the role of afadin in this response.
Morphogenesis requires dynamic coordination between cell-cell adhesion and the cytoskeleton to allow cells to change shape and move without losing tissue integrity. We used genetic tools and superresolution microscopy in a simple model epithelial cell line to define how the molecular architecture of cell-cell zonula adherens (ZA) is modified in response to elevated contractility, and how these cells maintain tissue integrity. We previously found that depleting zonula occludens 1 (ZO-1) family proteins in MDCK cells induces a highly organized contractile actomyosin array at the ZA. We find that ZO knockdown elevates contractility via a Shroom3/Rho-associated, coiled-coil containing protein kinase (ROCK) pathway. Our data suggest that each bicellular border is an independent contractile unit, with actin cables anchored end-on to cadherin complexes at tricellular junctions. Cells respond to elevated contractility by increasing junctional afadin. Although ZO/afadin knockdown did not prevent contractile array assembly, it dramatically altered cell shape and barrier function in response to elevated contractility. We propose that afadin acts as a robust protein scaffold that maintains ZA architecture at tricellular junctions.
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 peifer@unc.edu fanningalan@gmail.com wchoi@email.unc.edu.
Wangsun
W
Choi
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia 4072.
Bipul R
BR
Acharya
Institut Jacques Monod, Centre National de la Recherche Scientifique UMR 7592 and Université Paris Diderot, 75013 Paris, France.
Grégoire
G
Peyret
Institut Jacques Monod, Centre National de la Recherche Scientifique UMR 7592 and Université Paris Diderot, 75013 Paris, France.
Marc-Antoine
MA
Fardin
Institut Jacques Monod, Centre National de la Recherche Scientifique UMR 7592 and Université Paris Diderot, 75013 Paris, France.
René-Marc
RM
Mège
Institut Jacques Monod, Centre National de la Recherche Scientifique UMR 7592 and Université Paris Diderot, 75013 Paris, France Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
Benoit
B
Ladoux
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia 4072.
Alpha S
AS
Yap
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Alan S
AS
Fanning
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 peifer@unc.edu fanningalan@gmail.com wchoi@email.unc.edu.
Mark
M
Peifer
D008841:Actin Cytoskeleton / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D061985:Madin Darby Canine Kidney Cells; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D009024:Morphogenesis; D062825:Zonula Occludens Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D008840:Microfilament Proteins; D062825:Zonula Occludens Proteins; C108835:afadin