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Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration

Abstract : Actin filaments generate mechanical forces that drive membrane movements during trafficking, endocytosis and cell migration. Reciprocally, adaptations of actin networks to forces regulate their assembly and architecture. Yet, a demonstration of forces acting on actin regulators at actin assembly sites in cells is missing. Here we show that local forces arising from actin filament elongation mechanically control WAVE regulatory complex (WRC) dynamics and function, that is, Arp2/3 complex activation in the lamellipodium. Single-protein tracking revealed WRC lateral movements along the lamellipodium tip, driven by elongation of actin filaments and correlating with WRC turnover. The use of optical tweezers to mechanically manipulate functional WRC showed that piconewton forces, as generated by single-filament elongation, dissociated WRC from the lamellipodium tip. WRC activation correlated with its trapping, dwell time and the binding strength at the lamellipodium tip. WRC crosslinking, hindering its mechanical dissociation, increased WRC dwell time and Arp2/3-dependent membrane protrusion. Thus, forces generated by individual actin filaments on their regulators can mechanically tune their turnover and hence activity during cell migration.
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Contributor : Alexis Gautreau Connect in order to contact the contributor
Submitted on : Friday, October 7, 2022 - 7:51:03 AM
Last modification on : Saturday, October 8, 2022 - 3:51:11 AM

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Amine Mehidi, Frieda Kage, Zeynep Karatas, Maureen Cercy, Matthias Schaks, et al.. Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration. Nature Cell Biology, 2021, 23 (11), pp.1148-1162. ⟨10.1038/s41556-021-00786-8⟩. ⟨hal-03804973⟩



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