Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.
Rho and rac, two members of the ras-related superfamily of small GTPases, regulate the polymerization of actin to produce stress fibers and lamellipodia, respectively. We report here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia. In addition to stress fibers, rho controls the assembly of focal adhesion complexes. We now show that rac and cdc42 also stimulate the assembly of multimolecular focal complexes at the plasma membrane. These complexes, which are associated with lamellipodia and filopodia, contain vinculin, paxillin, and focal adhesion kinase, but are distinct from and formed independently of rho-induced focal adhesions. Activation of cdc42 in Swiss 3T3 cells leads to the sequential activation of rac and then rho, suggesting a molecular model for the coordinated control of cell motility by members of the rho family of GTPases.
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Cancer Research Campaign, University College London, England.
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D016475:3T3 Cells / Q000166:cytology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005656:Fungal Proteins / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000494:pharmacology / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008845:Microinjections; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020744:rac GTP-Binding Proteins; D020743:rhoB GTP-Binding Protein
D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; D011993:Recombinant Fusion Proteins; D016596:Vinculin; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020744:rac GTP-Binding Proteins; D020743:rhoB GTP-Binding Protein