WAVE and Arp2/3 jointly inhibit filopodium formation by entering into a complex with mDia2

Lamellipodia/ruffles and filopodia are protruding organelles containing short and highly branched or long and unbranched actin filaments, respectively(1-3). the microscopic morphology, dynamic development and protein signature of both lamellipodia/ruffles and filopodia have been investigated(2,3); however, little is known about the mechanisms by which cells coordinate the formation of these actin-based extensions. Here, we show that WAVE holds mDia2 and the Arp2/3 complex in a multimolecular complex. WAVE- and Arp2/3-dependent ruffling induced by EGF does not require mDia2. Conversely, the emission of mDia2-dependent filopodia correlates with its disengagement from WAVe. Consistently, the ability of eGF, Cdc42 and serum to induce mDia2-dependent formation of filopodia is increased in the absence of either the WAVe/Abi1/Nap1/PIR121 (WANP) or the Arp2/3 complex. reintroduction of WAVE2 into WANP-complex knockdown cells markedly reduces filopodia formation independently of actin polymerization. thus, WAVe and the Arp2/3 complex jointly orchestrate different types of actin-based plasma membrane protrusions by promoting ruffling and inhibiting mDia2-induced filopodia.