The RhoGAP HUM-7/Myo9 integrates signals to modulate RHO-1/RhoA during embryonic morphogenesis in Caenorhabditiselegans

Development. 2018 Dec 3;145(23):dev168724. doi: 10.1242/dev.168724.

Abstract

During embryonic morphogenesis, cells and tissues undergo dramatic movements under the control of F-actin regulators. Our studies of epidermal cell migrations in developing Caenorhabditiselegans embryos have identified multiple plasma membrane signals that regulate the Rac GTPase, thus regulating WAVE and Arp2/3 complexes, to promote branched F-actin formation and polarized enrichment. Here, we describe a pathway that acts in parallel to Rac to transduce membrane signals to control epidermal F-actin through the GTPase RHO-1/RhoA. RHO-1 contributes to epidermal migration through effects on underlying neuroblasts. We identify signals to regulate RHO-1-dependent events in the epidermis. HUM-7, the C. elegans homolog of human MYO9A and MYO9B, regulates F-actin dynamics during epidermal migration. Genetics and biochemistry support that HUM-7 behaves as a GTPase-activating protein (GAP) for the RHO-1/RhoA and CDC-42 GTPases. Loss of HUM-7 enhances RHO-1-dependent epidermal cell behaviors. We identify SAX-3/ROBO as an upstream signal that contributes to attenuated RHO-1 activation through its regulation of HUM-7/Myo9. These studies identify a new role for RHO-1 during epidermal cell migration, and suggest that RHO-1 activity is regulated by SAX-3/ROBO acting on the RhoGAP HUM-7.

Keywords: Actin dynamics; Morphogenesis; RhoA signaling.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Axon Guidance
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Movement
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism*
  • Epidermis / metabolism
  • Epistasis, Genetic
  • GTP-Binding Proteins / metabolism
  • Larva / metabolism
  • Morphogenesis*
  • Muscles / metabolism
  • Phenotype
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • cdc-42 protein, C elegans
  • GTP-Binding Proteins
  • RHO-1 protein, C elegans
  • rho GTP-Binding Proteins