Rho1 regulates apoptosis via activation of the JNK signaling pathway at the plasma membrane

J Cell Biol. 2010 Apr 19;189(2):311-23. doi: 10.1083/jcb.200912010.

Abstract

Precisely controlled growth and morphogenesis of developing epithelial tissues require coordination of multiple factors, including proliferation, adhesion, cell shape, and apoptosis. RhoA, a small GTPase, is known to control epithelial morphogenesis and integrity through its ability to regulate the cytoskeleton. In this study, we examine a less well-characterized RhoA function in cell survival. We demonstrate that the Drosophila melanogaster RhoA, Rho1, promotes apoptosis independently of Rho kinase through its effects on c-Jun NH(2)-terminal kinase (JNK) signaling. In addition, Rho1 forms a complex with Slipper (Slpr), an upstream activator of the JNK pathway. Loss of Moesin (Moe), an upstream regulator of Rho1 activity, results in increased levels of Rho1 at the plasma membrane and cortical accumulation of Slpr. Together, these results suggest that Rho1 functions at the cell cortex to regulate JNK activity and implicate Rho1 and Moe in epithelial cell survival.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis / physiology*
  • Cell Membrane / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / physiology
  • Enzyme Activation
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • RNA Interference
  • Signal Transduction / physiology*
  • Wings, Animal / anatomy & histology
  • Wings, Animal / physiology
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Membrane Proteins
  • moesin, Drosophila
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • slpr protein, Drosophila
  • Rho1 protein, Drosophila
  • rho GTP-Binding Proteins