ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning

Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerg-ing aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform-specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.

Automated summary

Regulation of the Arp2/3 complex plays a crucial role in the nucleation of branched actin networks. Incorporation of subunit isoforms, such as ArpC5 and ArpC5L, fine-tunes nucleation activity and branch junction stability, affecting cell migration. Furthermore, ArpC5 isoforms impact the positioning of Ena/VASP proteins, which mediate isoform-specific effects on actin assembly and contribute to a signaling pathway enhancing cell migration.