Open AccessThe small GTPase RalA targets filamin to induce filopodia
Author(s) -
Yasutaka Ohta,
Naomichi Suzuki,
Shun Nakamura,
John H. Hartwig,
Thomas P. Stossel
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.5.2122
Subject(s) - filamin , filopodia , cdc42 , microbiology and biotechnology , flna , gtpase , small gtpase , actin cytoskeleton , lamellipodium , cytoskeleton , actin , ras superfamily , biology , chemistry , gtp' , signal transduction , biochemistry , cell , enzyme
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.