Abi1 is essential for the formation and activation of a WAVE2 signalling complex
| Autor: | Metello Innocenti, Andrea Disanza, Liliana B. Areces, Giorgio Scita, Pier Paolo Di Fiore, Adriana Zucconi, Anika Steffen, Emanuela Frittoli, Theresia E. B. Stradal, Marie-France Carlier |
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| Přispěvatelé: | Innocenti, M, Zucconi, A, Disanza, A, Frittoli, E, Areces, L, Steffen, A, Stradal, T, Di Fiore, P, Carlier, M, Scita, G |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
cell migration
Macromolecular Substances WAVE regulatory complex macromolecular substances Biology Cell Movement Humans Arp2/3 complex Pseudopodia Cytoskeleton Adaptor Proteins Signal Transducing Actin nucleation Microfilament Proteins cell signalling Cell Biology Actin cytoskeleton ABI1 Protein Structure Tertiary Wiskott-Aldrich Syndrome Protein Family rac GTP-Binding Proteins Cell biology Rac GTP-Binding Proteins Actin Cytoskeleton Cytoskeletal Proteins Actin-Related Protein 2 RNA Interference Lamellipodium Carrier Proteins actin HeLa Cells Signal Transduction |
| Popis: | WAVE2 belongs to a family of proteins that mediates actin reorganization by relaying signals from Rac to the Arp2/3 complex, resulting in lamellipodia protrusion. WAVE2 displays Arp2/3-dependent actin nucleation activity in vitro, and does not bind directly to Rac. Instead, it forms macromolecular complexes that have been reported to exert both positive and negative modes of regulation. How these complexes are assembled, localized and activated in vivo remains to be established. Here we use tandem mass spectrometry to identify an Abi1-based complex containing WAVE2, Nap1 (Nck-associated protein) and PIR121. Abi1 interacts directly with the WHD domain of WAVE2, increases WAVE2 actin polymerization activity and mediates the assembly of a WAVE2-Abi1-Nap1-PIR121 complex. The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. Thus, Abi1 orchestrates the proper assembly of the WAVE2 complex and mediates its activation at the leading edge in vivo. |
| Databáze: | OpenAIRE |
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