Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin-Related Protein 2-3 Complex / genetics
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Actin-Related Protein 2-3 Complex / metabolism*
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Epidermal Growth Factor / metabolism
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Formins
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HeLa Cells
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Humans
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Multiprotein Complexes / metabolism*
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Proteins / genetics
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Proteins / metabolism
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Pseudopodia / metabolism*
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Pseudopodia / ultrastructure
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Wiskott-Aldrich Syndrome Protein Family / genetics
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Wiskott-Aldrich Syndrome Protein Family / metabolism*
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism
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tRNA Methyltransferases
Substances
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Actin-Related Protein 2-3 Complex
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Carrier Proteins
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DIAPH2 protein, human
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Formins
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Multiprotein Complexes
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Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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Wiskott-Aldrich Syndrome Protein Family
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Epidermal Growth Factor
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TRMO protein, human
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tRNA Methyltransferases
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins