Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation

Nat Cell Biol. 2011 Jun 19;13(7):860-6. doi: 10.1038/ncb2274.


Apical-domain constriction is important for regulating epithelial morphogenesis. Epithelial cells are connected by apical junctional complexes (AJCs) that are lined with circumferential actomyosin cables. The contractility of these cables is regulated by Rho-associated kinases (ROCKs). Here, we report that Willin (a FERM-domain protein) and Par3 (a polarity-regulating protein) cooperatively regulate ROCK-dependent apical constriction. We found that Willin recruits aPKC and Par6 to the AJCs, independently of Par3. Simultaneous depletion of Willin and Par3 completely removed aPKC and Par6 from the AJCs and induced apical constriction. Induced constriction was through upregulation of the level of AJC-associated ROCKs, which was due to loss of aPKC. Our results indicate that aPKC phosphorylates ROCK and suppresses its junctional localization, thereby allowing cells to retain normally shaped apical domains. Thus, we have uncovered a Willin/Par3-aPKC-ROCK pathway that controls epithelial apical morphology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Cycle Proteins
  • Cell Shape*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Dogs
  • Epithelial Cells / enzymology*
  • HEK293 Cells
  • Humans
  • Intercellular Junctions / enzymology*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Mice
  • Mutation
  • Nerve Tissue Proteins
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • RNA Interference
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Transfection
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Isoenzymes
  • Nerve Tissue Proteins
  • PARD6A protein, human
  • Pard3 protein, mouse
  • Pard3 protein, rat
  • Recombinant Fusion Proteins
  • Rock1 protein, mouse
  • rho-Associated Kinases
  • Protein Kinase C
  • protein kinase C lambda