Abl and Canoe/Afadin mediate mechanotransduction at tricellular junctions

Science. 2020 Nov 27;370(6520):eaba5528. doi: 10.1126/science.aba5528.

Abstract

Epithelial structure is generated by the dynamic reorganization of cells in response to mechanical forces. Adherens junctions transmit forces between cells, but how cells sense and respond to these forces in vivo is not well understood. We identify a mechanotransduction pathway involving the Abl tyrosine kinase and Canoe/Afadin that stabilizes cell adhesion under tension at tricellular junctions in the Drosophila embryo. Canoe is recruited to tricellular junctions in response to actomyosin contractility, and this mechanosensitivity requires Abl-dependent phosphorylation of a conserved tyrosine in the Canoe actin-binding domain. Preventing Canoe tyrosine phosphorylation destabilizes tricellular adhesion, and anchoring Canoe at tricellular junctions independently of mechanical inputs aberrantly stabilizes adhesion, arresting cell rearrangement. These results identify a force-responsive mechanism that stabilizes tricellular adhesion under tension during epithelial remodeling.

Publication types

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

MeSH terms

  • Actomyosin / physiology
  • Animals
  • Cell Adhesion*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Embryo, Nonmammalian
  • Intercellular Junctions / genetics
  • Intercellular Junctions / physiology*
  • Mechanotransduction, Cellular*
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Drosophila Proteins
  • cno protein, Drosophila
  • Actomyosin
  • Protein-Tyrosine Kinases
  • Abl protein, Drosophila