Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis

J Cell Biol. 2017 Nov 6;216(11):3729-3744. doi: 10.1083/jcb.201611061. Epub 2017 Sep 13.

Abstract

During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis.

Publication types

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

MeSH terms

  • Actins / metabolism*
  • Adherens Junctions / enzymology*
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Polarity*
  • Embryo, Nonmammalian / enzymology
  • Epidermis / embryology
  • Epidermis / enzymology*
  • Epithelial Cells / enzymology*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Genotype
  • Morphogenesis
  • Mutation
  • Phenotype
  • Signal Transduction
  • Time Factors

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • GTPase-Activating Proteins
  • PAC-1 protein, C elegans
  • cdc-42 protein, C elegans
  • rho GTPase-activating protein
  • GTP-Binding Proteins