The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin

Nat Cell Biol. 2000 Dec;2(12):888-92. doi: 10.1038/35046533.

Abstract

Rho GTPases control actin reorganization and many other cellular functions. Guanine nucleotide-exchange factors (GEFs) activate Rho GTPases by promoting their exchange of GDP for GTP. Trio is a unique Rho GEF, because it has separate GEF domains, GEFD1 and GEFD2, that control the GTPases RhoG/Rac1 and RhoA, respectively. Dbl-homology (DH) domains that are common to GEFs catalyse nucleotide exchange, and pleckstrin-homology (PH) domains localize Rho GEFs near their downstream targets. Here we show that Trio GEFD1 interacts through its PH domain with the actin-filament-crosslinking protein filamin, and localizes with endogenous filamin in HeLa cells. Trio GEFD1 induces actin-based ruffling in filamin-expressing, but not filamin-deficient, cells and in cells transfected with a filamin construct that lacks the Trio-binding domain. In addition, Trio GEFD1 exchange activity is not affected by filamin binding. Our results indicate that filamin, as a molecular target of Trio, may be a scaffold for the spatial organization of Rho-GTPase-mediated signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Contractile Proteins / genetics
  • Contractile Proteins / metabolism*
  • Cytoskeleton / metabolism
  • Filamins
  • GTP Phosphohydrolases / metabolism*
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • HeLa Cells
  • Humans
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Transfection
  • rac1 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins

Substances

  • Actins
  • Contractile Proteins
  • Filamins
  • Guanine Nucleotide Exchange Factors
  • Microfilament Proteins
  • Phosphoproteins
  • RHOG protein, human
  • Protein-Serine-Threonine Kinases
  • TRIO protein, human
  • GTP Phosphohydrolases
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins