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Arf6 Can Trigger Wave Regulatory Complex-Dependent Actin Assembly Independent of Arno

Published version
Peer-reviewed

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Authors

Singh, Vikash 
Davidson, Anthony C. 
Hume, Peter J. 
Koronakis, Vassilis 

Abstract

The small GTPase ADP-ribosylation factor 6 (Arf6) anchors at the plasma membrane to orchestrate key functions, such as membrane trafficking and regulating cortical actin cytoskeleton rearrangement. A number of studies have identified key players that interact with Arf6 to regulate actin dynamics in diverse cell processes, yet it is still unknown whether Arf6 can directly signal to the wave regulatory complex to mediate actin assembly. By reconstituting actin dynamics on supported lipid bilayers, we found that Arf6 in co-ordination with Rac1(Ras-related C3 botulinum toxin substrate 1) can directly trigger actin polymerization by recruiting wave regulatory complex components. Interestingly, we demonstrated that Arf6 triggers actin assembly at the membrane directly without recruiting the Arf guanine nucleotide exchange factor (GEF) ARNO (ARF nucleotide-binding site opener), which is able to activate Arf1 to enable WRC-dependent actin assembly. Furthermore, using labelled E. coli, we demonstrated that actin assembly by Arf6 also contributes towards efficient phagocytosis in THP-1 macrophages. Taken together, this study reveals a mechanism for Arf6-driven actin polymerization.

Description

Keywords

Arf GTPases, actin cytoskeleton, wave regulatory complex, phagocytosis, macrophages, host–pathogen interplay

Journal Title

International Journal of Molecular Sciences

Conference Name

Journal ISSN

1422-0067

Volume Title

21

Publisher

MDPI
Sponsorship
Wellcome Trust (101828/Z/13/Z)
Medical Research Council (MR/L008122/1)