CGEF-1 and CHIN-1 regulate CDC-42 activity during asymmetric division in the Caenorhabditis elegans embryo

Mol Biol Cell. 2010 Jan 15;21(2):266-77. doi: 10.1091/mbc.e09-01-0060. Epub 2009 Nov 18.

Abstract

The anterior-posterior axis of the Caenorhabditis elegans embryo is elaborated at the one-cell stage by the polarization of the partitioning (PAR) proteins at the cell cortex. Polarization is established under the control of the Rho GTPase RHO-1 and is maintained by the Rho GTPase CDC-42. To understand more clearly the role of the Rho family GTPases in polarization and division of the early embryo, we constructed a fluorescent biosensor to determine the localization of CDC-42 activity in the living embryo. A genetic screen using this biosensor identified one positive (putative guanine nucleotide exchange factor [GEF]) and one negative (putative GTPase activating protein [GAP]) regulator of CDC-42 activity: CGEF-1 and CHIN-1. CGEF-1 was required for robust activation, whereas CHIN-1 restricted the spatial extent of CDC-42 activity. Genetic studies placed CHIN-1 in a novel regulatory loop, parallel to loop described previously, that maintains cortical PAR polarity. We found that polarized distributions of the nonmuscle myosin NMY-2 at the cell cortex are independently produced by the actions of RHO-1, and its effector kinase LET-502, during establishment phase and CDC-42, and its effector kinase MRCK-1, during maintenance phase. CHIN-1 restricted NMY-2 recruitment to the anterior during maintenance phase, consistent with its role in polarizing CDC-42 activity during this phase.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Division*
  • Cell Polarity
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / metabolism
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / genetics
  • Myosin Type II / metabolism
  • Protein Binding
  • Protein Transport
  • Signal Transduction
  • cdc42 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • CGEF-1 protein, C elegans
  • CHIN-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Green Fluorescent Proteins
  • Myosin Type II
  • cdc42 GTP-Binding Protein
  • rho GTP-Binding Proteins