Rap1 Spatially Controls ArhGAP29 To Inhibit Rho Signaling during Endothelial Barrier Regulation

Mol Cell Biol. 2015 Jul;35(14):2495-502. doi: 10.1128/MCB.01453-14. Epub 2015 May 11.

Abstract

The small GTPase Rap1 controls the actin cytoskeleton by regulating Rho GTPase signaling. We recently established that the Rap1 effectors Radil and Rasip1, together with the Rho GTPase activating protein ArhGAP29, mediate Rap1-induced inhibition of Rho signaling in the processes of epithelial cell spreading and endothelial barrier function. Here, we show that Rap1 induces the independent translocations of Rasip1 and a Radil-ArhGAP29 complex to the plasma membrane. This results in the formation of a multimeric protein complex required for Rap1-induced inhibition of Rho signaling and increased endothelial barrier function. Together with the previously reported spatiotemporal control of the Rap guanine nucleotide exchange factor Epac1, these findings elucidate a signaling pathway for spatiotemporal control of Rho signaling that operates by successive protein translocations to and complex formation at the plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Intercellular Junctions / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Microscopy, Confocal
  • Protein Binding
  • Protein Transport
  • RNA Interference
  • Signal Transduction*
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • ARHGAP29 protein, human
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • RADIL protein, human
  • RAPGEF3 protein, human
  • RASIP1 protein, human
  • rap1 GTP-Binding Proteins
  • rho GTP-Binding Proteins