Imperial College London
Professor Michael Way

ProfessorMichaelWay

Faculty of Medicine, Department of Infectious Disease

Professor of Virology
 
 
 
//

Contact

 

+44 (0)20 3796 2068michael.way1 Website

 
 
//

Location

 

Francis Crick InstituteThe Francis Crick Institute

//

Summary

 

Publications

Citation

BibTex format

@article{Cao:2022:10.1101/2022.05.06.490861,
author = {Cao, L and Ghasemi, F and Way, M and Jégou, A and Romet-Lemonne, G},
doi = {10.1101/2022.05.06.490861},
title = {Nucleation and stability of branched versus linear Arp2/3-generated actin filaments},
url = {http://dx.doi.org/10.1101/2022.05.06.490861},
year = {2022}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:p>Activation of the Arp2/3 complex by VCA-domain-bearing NPFs results in the formation of ‘daughter’ actin filaments branching off the sides of pre-existing ‘mother filaments.’ Alternatively, when stimulated by SPIN90, Arp2/3 directly nucleates ‘linear’ actin filaments. Uncovering the similarities and differences of these two activation mechanisms is fundamental to understanding the regulation and function of Arp2/3. Analysis of individual filaments reveals that the catalytic VCA domain of WASP, N-WASP and WASH, accelerate the Arp2/3-mediated nucleation of linear filaments by SPIN90, in addition to their known branch-promoting activity. Unexpectedly, these VCA domains also destabilize existing branches, as well as SPIN90-Arp2/3 at filament pointed ends. Furthermore, cortactin and GMF, which respectively stabilize and destabilize Arp2/3 at branch junctions, have a similar impact on SPIN90-activated Arp2/3. However, unlike branch junctions, SPIN90-Arp2/3 at the pointed end of linear filaments is not destabilized by piconewton forces, and does not become less stable with time. It thus appears that linear and branched Arp2/3-generated filaments respond similarly to regulatory proteins, albeit with quantitative differences, and that they differ greatly in their responses to aging and to mechanical stress. These results indicate that SPIN90- and VCA-activated Arp2/3 complexes adopt similar yet non-identical conformations, and that their turnover in cells may be regulated differently.</jats:p>
AU  - Cao,L
AU  - Ghasemi,F
AU  - Way,M
AU  - Jégou,A
AU  - Romet-Lemonne,G
DO  - 10.1101/2022.05.06.490861
PY  - 2022///
TI  - Nucleation and stability of branched versus linear Arp2/3-generated actin filaments
UR  - http://dx.doi.org/10.1101/2022.05.06.490861
ER  -
Download