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• W2051038367 abstract "Arp2/3 complex is an important actin filament nucleator that creates branched actin filament networks required for formation of lamellipodia and endocytic actin structures. Cellular assembly of branched actin networks frequently requires multiple Arp2/3 complex activators, called nucleation promoting factors (NPFs). We recently presented a mechanism by which cortactin, a weak NPF, can displace a more potent NPF, N-WASP, from nascent branch junctions to synergistically accelerate nucleation. The distinct roles of these NPFs in branching nucleation are surprising given their similarities. We biochemically dissected these two classes of NPFs to determine how their Arp2/3 complex and actin interacting segments modulate their influences on branched actin networks. We find that the Arp2/3 complex-interacting N-terminal acidic sequence (NtA) of cortactin has structural features distinct from WASP acidic regions (A) that are required for synergy between the two NPFs. Our mutational analysis shows that differences between NtA and A do not explain the weak intrinsic NPF activity of cortactin, but instead that cortactin is a weak NPF because it cannot recruit actin monomers to Arp2/3 complex. We use TIRF microscopy to show that cortactin bundles branched actin filaments using actin filament binding repeats within a single cortactin molecule, but that N-WASP antagonizes cortactin-mediated bundling. Finally, we demonstrate that multiple WASP family proteins synergistically activate Arp2/3 complex and determine the biochemical requirements in WASP proteins for synergy. Our data indicate that synergy between WASP proteins and cortactin may play a general role in assembling diverse actin-based structures, including lamellipodia, podosomes, and endocytic actin networks." @default.
• W2051038367 created "2016-06-24" @default.
• W2051038367 creator A5000951142 @default.
• W2051038367 creator A5031040552 @default.
• W2051038367 creator A5040327626 @default.
• W2051038367 creator A5061563381 @default.
• W2051038367 creator A5080073838 @default.
• W2051038367 date "2014-10-01" @default.
• W2051038367 modified "2023-10-13" @default.
• W2051038367 title "Interactions with Actin Monomers, Actin Filaments, and Arp2/3 Complex Define the Roles of WASP Family Proteins and Cortactin in Coordinately Regulating Branched Actin Networks" @default.
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• W2051038367 doi "https://doi.org/10.1074/jbc.m114.587527" @default.
• W2051038367 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4200246" @default.
• W2051038367 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25160634" @default.
• W2051038367 hasPublicationYear "2014" @default.
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