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. The microscopic morphology, dynamic development and protein signature of both lamellipodia/ruffles and filopodia have been investigated; 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.
Institute of Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Petra
P
Beli
Debora
D
Mascheroni
Dalu
D
Xu
Metello
M
Innocenti
D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012359:tRNA Methyltransferases
D051376:Actin-Related Protein 2-3 Complex; D002352:Carrier Proteins; C491462:DIAPH2 protein, human; D000080865:Formins; D046912:Multiprotein Complexes; D011506:Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; D004815:Epidermal Growth Factor; C498548:TRMO protein, human; D012359:tRNA Methyltransferases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins