Key result
Arp2/3 activation by N-WASP or WAVE2 boosts actin branching efficiency ~100% versus VCA alone.
Why the study?
The mechanism by which N-WASP and WAVE2 enhance branching efficiency of actin filaments via Arp2/3 complex activation was unclear.
The actin filament binding activity of N-WASP and WAVE2 in the basic region increases branching efficiency on pre-existing ADP filaments, which may be important for initiation of actin-based motility.
Answers are grounded in this paper and cite their sources.
May enhance actin motility models; leaves open relevance to cardiovascular cytoskeletal dynamics.
The actin-related protein (Arp) 2/3 complex is an essential regulator of de novo actin filament formation. Arp2/3 nucleates the polymerization of actin and creates branched actin filaments when activated by Arp2/3-complex activating domain (VCA) of Wiskott-Aldrich syndrome proteins (WASP family proteins). We found that the branching of actin filaments on pre-existing ADP filaments mediated by the Arp2/3 complex is twice as efficient when Arp2/3 was activated by wild-type neural WASP (N-WASP) or WASP-family verprolin-homologous protein (WAVE) 2 than when activated by the VCA domain alone. By contrast, there was no difference between wild-type N-WASP or WAVE2 and VCA in the branching efficiency on de novo filaments, which are thought to consist mainly of ADP-phosphate filaments. This increased branching efficiency on ADP filaments is due to the basic region located in the center of N-WASP and WAVE2, which was found to associate with ADP actin filaments. Actin filaments and phosphatidylinositol bisphosphate (PIP2) associate with N-WASP at different sites. This association of N-WASP and WAVE2 with actin filaments enhanced recruitment of Arp2/3 to the pre-existing filaments, presumably leading to efficient nucleation and branch formation on pre-existing filaments. These data together suggest that the actin filament binding activity of N-WASP and WAVE2 in the basic region increases the number of barbed ends created on pre-existing filaments. Efficient branching on ADP filaments may be important for initiation of actin-based motility.
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Suetsugu et al. (2001) studied this question. Wild-type neural WASP (N-WASP) or WAVE2 vs. VCA domain alone was evaluated on Branching efficiency of actin filaments on pre-existing ADP filaments (twice as efficient). Activation of Arp2/3 by wild-type N-WASP or WAVE2 made branching of actin filaments on pre-existing ADP filaments twice as efficient compared to activation by the VCA domain alone.
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