Membrane targeting of WAVE2 is not sufficient for WAVE2-dependent actin polymerization: a role for IRSp53 in mediating the interaction between Rac and WAVE2

• DOI: 10.1242/jcs.010272
• Publication Date: 2008-01-16T03:32:31Z
• Authors: Wassim Abou-Kheir; Beth Isaac; Hideki Yamaguchi; Dianne Cox
• Keywords: Pseudopodia; Filopodia; Rac GTP-Binding Proteins; Podosome; Actin-binding protein

Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous (WAVE) proteins play a major role in Rac-induced actin dynamics, but Rac does not bind directly to WAVE proteins. It has been proposed that either the insulin receptor substrate 53 (IRSp53) or complex of containing Abelson interactor 1 (Abi1) mediates interaction WAVE2 and Rac. Depletion endogenous IRSp53 by RNA-mediated interference (RNAi) RAW/LR5 macrophage cell line resulted significant reduction Rac1Q61L-induced surface ruffles colony-stimulating factor (CSF-1)-induced polymerization, protrusion migration. However, was essential for Fcgamma-R-mediated phagocytosis, formation podosomes Cdc42V12-induced filopodia. found be present an immunoprecipitable with Abi1 Rac1-activation-dependent manner cells vivo. Importantly, expression lacking WAVE2-binding site (IRSp53DeltaSH3) association Rac1 Abi1, indicating is dependent. While it activity regulated membrane recruitment, targeting Cos-7 did induce polymerization protrusion, suggesting recruitment insufficient regulation WAVE2. Combined, these data suggest links vivo its function crucial production CSF-1-induced F-actin-rich protrusions migration macrophages. This study indicates Rac1, along involved more tight than one operating solely through localization.