Abstract
SummaryEna/VASP proteins and the WAVE regulatory complex (WRC) regulate cell motility by virtue of their ability to independently promote actin polymerization. We demonstrate that Ena/VASP and the WRC control actin polymerization in a cooperative manner through the interaction of the Ena/VASP EVH1 domain with an extended proline rich motif in Abi. This interaction increases cell migration and enables VASP to cooperatively enhance WRC stimulation of Arp2/3 complex-mediated actin assembly in vitro in the presence of Rac. Loss of this interaction in Drosophila macrophages results in defects in lamellipodia formation, cell spreading, and redistribution of Ena to the tips of filopodia-like extensions. Rescue experiments of abi mutants also reveals a physiological requirement for the Abi:Ena interaction in photoreceptor axon targeting and oogenesis. Our data demonstrate that the activities of Ena/VASP and the WRC are intimately linked to ensure optimal control of actin polymerization during cell migration and development.
Highlights
We demonstrate that Ena/VASP and the WAVE regulatory complex (WRC) control actin polymerization in a cooperative manner through the interaction of the Ena/VASP EVH1 domain with an extended proline rich motif in Abi
Our data demonstrate that the activities of Ena/VASP and the WRC are intimately linked to ensure optimal control of actin polymerization during cell migration and development
We found that the EVH1 domain interacts directly with Abi, a component of the WAVE regulatory complex (WRC), which plays an essential role in driving cell migration by activating the Arp2/3 complex in response to Rac signaling (Bisi et al, 2013)
Summary
Ena/VASP proteins regulate cell migration by promoting actin polymerization at the plasma membrane via antagonizing actin filament capping and acting as processive actin polymerases (Barzik et al, 2005; Bear et al, 2002; Breitsprecher et al, 2008, 2011; Hansen and Mullins, 2010; Pasic et al, 2008). The EVH2 domain, which contains monomeric and F-actin binding sites, is responsible for promoting actin polymerization (Barzik et al, 2005; Breitsprecher et al, 2008, 2011; Pasic et al, 2008). The ability of Ena/VASP proteins to control cell migration, depends on their recruitment to the leading edge (Bear et al, 2000, 2002), by ‘‘FPPPP’’ motif containing MRL proteins (Mig, RIAM, and Lamellipodin; Coloet al., 2012; Jenzora et al, 2005; Krause et al, 2004; Lafuente et al, 2004; Quinn et al, 2006)
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