The small GTPase RalA targets filamin to induce filopodia.
The Ras-related small GTPases Rac, Rho, Cdc42, and RalA bind filamin, an actin filament-crosslinking protein that also links membrane and other intracellular proteins to actin. Of these GTPases only RalA binds filamin in a GTP-specific manner, and GTP-RalA elicits actin-rich filopods on surfaces of Swiss 3T3 cells and recruits filamin ... into the filopodial cytoskeleton. Either a dominant negative RalA construct or the RalA-binding domain of filamin 1 specifically block Cdc42-induced filopod formation, but a Cdc42 inhibitor does not impair RalA's effects, which, unlike Cdc42, are Rac independent. RalA does not generate filopodia in filamin-deficient human melanoma cells, whereas transfection of filamin 1 restores the functional response. RalA therefore is a downstream intermediate in Cdc42-mediated filopod production and uses filamin in this pathway.
Mesh Terms:
3T3 Cells, Actins, Animals, COS Cells, Carrier Proteins, Cloning, Molecular, Contractile Proteins, Cytoskeleton, Escherichia coli, GTP Phosphohydrolases, Humans, Kinetics, Membrane Proteins, Mice, Microfilament Proteins, Microscopy, Video, Pseudopodia, Recombinant Fusion Proteins, Recombinant Proteins, Time Factors, Transfection, ral GTP-Binding Proteins
3T3 Cells, Actins, Animals, COS Cells, Carrier Proteins, Cloning, Molecular, Contractile Proteins, Cytoskeleton, Escherichia coli, GTP Phosphohydrolases, Humans, Kinetics, Membrane Proteins, Mice, Microfilament Proteins, Microscopy, Video, Pseudopodia, Recombinant Fusion Proteins, Recombinant Proteins, Time Factors, Transfection, ral GTP-Binding Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 02, 1999
PubMed ID: 10051605
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