Arf6 Can Trigger Wave Regulatory Complex-Dependent Actin Assembly Independent of Arno.
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Authors
Singh, Vikash
Davidson, Anthony C
Hume, Peter J
Koronakis, Vassilis
Publication Date
2020-04-02Journal Title
International journal of molecular sciences
ISSN
1422-0067
Volume
21
Issue
7
Language
eng
Type
Article
This Version
VoR
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Singh, V., Davidson, A. C., Hume, P. J., & Koronakis, V. (2020). Arf6 Can Trigger Wave Regulatory Complex-Dependent Actin Assembly Independent of Arno.. International journal of molecular sciences, 21 (7) https://doi.org/10.3390/ijms21072457
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.
Keywords
Macrophages, Phagocytosis, Actin cytoskeleton, Arf Gtpases, Wave Regulatory Complex, Host–pathogen Interplay
Sponsorship
Medical Research Council (MR/L008122/1)
Wellcome Trust (101828/Z/13/Z)
Identifiers
PMC7177560, 32252226
External DOI: https://doi.org/10.3390/ijms21072457
This record's URL: https://www.repository.cam.ac.uk/handle/1810/305158
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