SPIN90 modulates the architecture of lamellipodial actin in an ARPC5L dependent fashion.

When stimulated by nucleation-promoting factors such as WAVE, the Arp2/3 complex generates branched actin networks. In contrast, when activated by SPIN90, the Arp2/3 complex generates linear actin filaments. The Arp2/3 complex in mammals, consists of 8 iso-complexes with different properties as there are two isoforms of Arp3, ArpC1 and ArpC5. Here, using recombinant Arp2/3 iso-complexes with defined composition, we show that SPIN90 selectively activates ArpC5L rather than ArpC5 containing complexes to generate linear actin filaments. Consistent with this, SPIN90 at the leading edge of migrating cells enhances the recruitment of ArpC5L but not ArpC5 containing Arp2/3 complexes to lamellipodia. These SPIN90-Arp2/3-ArpC5L complexes generate linear actin filaments that integrate into lamellipodia and impact protrusion efficiency. Moreover, loss of SPIN90 leads to an enrichment in actin filaments that are more perpendicular to the plasma membrane. Our results demonstrate that SPIN90 regulates the architecture and dynamics of lamellipodial actin in an Arp2/3 iso-complex dependent fashion. TeaserSPIN90 selectively recruits and activates ArpC5L containing Arp2/3 to shape the architecture and dynamics of lamellipodial actin.