srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization

J Biol Chem. 2010 Nov 5;285(45):35133-41. doi: 10.1074/jbc.M110.153429. Epub 2010 Sep 1.

Abstract

The Slit-Robo GTPase-activating proteins (srGAPs) are critical for neuronal migration through inactivation of Rho GTPases Cdc42, Rac1, and RhoA. Here we report that srGAP2 physically interacts with protein arginine methyltransferase 5 (PRMT5). srGAP2 localizes to the cytoplasm and plasma membrane protrusion. srGAP2 knockdown reduces cell adhesion spreading and increases cell migration, but has no effect on cell proliferation. PRMT5 binds to the N terminus of srGAP2 (225-538 aa) and methylates its C-terminal arginine residue Arg-927. The methylation mutant srGAP2-R927A fails to rescue the cell spreading rate, is unable to localize to the plasma membrane leading edge, and perturbs srGAP2 homodimer formation mediated by the F-BAR domain. These results suggest that srGAP2 arginine methylation plays important roles in cell spreading and cell migration through influencing membrane protrusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Arginine / genetics
  • Arginine / metabolism
  • CHO Cells
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cell Movement / physiology*
  • Cell Proliferation
  • Cricetinae
  • Cricetulus
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Methylation
  • Mutation, Missense
  • Protein Methyltransferases / genetics
  • Protein Methyltransferases / metabolism
  • Protein Multimerization / physiology*
  • Protein-Arginine N-Methyltransferases
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • GTPase-Activating Proteins
  • RAC1 protein, human
  • SRGAP2 protein, human
  • RHOA protein, human
  • Arginine
  • Protein Methyltransferases
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein