The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin.
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.
Bellanger
J M
JM
CRBM-CNRS, UPR 1086, 1919 Route de Mende, 34293 Montpellier Cédex 5, France.
Astier
C
C
Sardet
C
C
Ohta
Y
Y
Stossel
T P
TP
Debant
A
A
D000199:Actins / Q000378:metabolism*; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D064448:Filamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020741:rho GTP-Binding Proteins
D000199:Actins; D003285:Contractile Proteins; D064448:Filamins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D010750:Phosphoproteins; C075397:RHOG protein, human; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human; D020558:GTP Phosphohydrolases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins