DAPLE orchestrates apical actomyosin assembly from junctional polarity complexes

J Cell Biol. 2022 May 2;221(5):e202111002. doi: 10.1083/jcb.202111002. Epub 2022 Apr 7.

Abstract

Establishment of apicobasal polarity and the organization of the cytoskeleton must operate coordinately to ensure proper epithelial cell shape and function. However, the precise molecular mechanisms by which polarity complexes directly instruct the cytoskeletal machinery to determine cell shape are poorly understood. Here, we define a mechanism by which the PAR polarity complex (PAR3-PAR6-aPKC) at apical cell junctions leads to efficient assembly of the apical actomyosin network to maintain epithelial cell morphology. We found that the PAR polarity complex recruits the protein DAPLE to apical cell junctions, which in turn triggers a two-pronged mechanism that converges upon assembly of apical actomyosin. More specifically, DAPLE directly recruits the actin-stabilizing protein CD2AP to apical junctions and, concomitantly, activates heterotrimeric G protein signaling in a GPCR-independent manner to favor RhoA-myosin activation. These observations establish DAPLE as a direct molecular link between junctional polarity complexes and the formation of apical cytoskeletal assemblies that support epithelial cell shape.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Actomyosin* / metabolism
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Polarity*
  • Cell Shape
  • Cytoskeletal Proteins / metabolism
  • Epithelial Cells / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins* / metabolism
  • Microfilament Proteins* / metabolism
  • Protein Kinase C / metabolism

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Actomyosin
  • Protein Kinase C
  • Heterotrimeric GTP-Binding Proteins