Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Cell Biology Année : 2021

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

Résumé

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.

Dates et versions

hal-03804973 , version 1 (07-10-2022)

Identifiants

Citer

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⟩
27 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More