Buracco, Simona;
Doring, Hermann;
Engelbart, Stefanie;
Singh, Shashi Prakash;
Paschke, Peggy;
Whitelaw, Jamie;
Thomason, Peter A;
... Insall, Robert H; + view all
(2024)
Scar/WAVE drives actin protrusions independently of its VCA domain using proline-rich domains.
Current Biology
, 34
(19)
4436-4451.e9.
10.1016/j.cub.2024.08.013.
Preview |
Text
Insall_1-s2.0-S0960982224011254-main.pdf Download (9MB) | Preview |
Abstract
Cell migration requires the constant modification of cellular shape by reorganization of the actin cytoskeleton. Fine-tuning of this process is critical to ensure new actin filaments are formed only at specific times and in defined regions of the cell. The Scar/WAVE complex is the main catalyst of pseudopod and lamellipodium formation during cell migration. It is a pentameric complex highly conserved through eukaryotic evolution and composed of Scar/WAVE, Abi, Nap1/NCKAP1, Pir121/CYFIP, and HSPC300/Brk1. Its function is usually attributed to activation of the Arp2/3 complex through Scar/WAVE’s VCA domain, while other parts of the complex are expected to mediate spatial-temporal regulation and have no direct role in actin polymerization. Here, we show in both B16-F1 mouse melanoma and Dictyostelium discoideum cells that Scar/WAVE without its VCA domain still induces the formation of morphologically normal, actin-rich protrusions, extending at comparable speeds despite a drastic reduction of Arp2/3 recruitment. However, the proline-rich regions in Scar/WAVE and Abi subunits are essential, though either is sufficient for the generation of actin protrusions in B16-F1 cells. We further demonstrate that N-WASP can compensate for the absence of Scar/WAVE’s VCA domain and induce lamellipodia formation, but it still requires an intact WAVE complex, even if without its VCA domain. We conclude that the Scar/WAVE complex does more than directly activating Arp2/3, with proline-rich domains playing a central role in promoting actin protrusions. This implies a broader function for the Scar/WAVE complex, concentrating and simultaneously activating many actin-regulating proteins as a lamellipodium-producing core.
| Type: | Article |
|---|---|
| Title: | Scar/WAVE drives actin protrusions independently of its VCA domain using proline-rich domains |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cub.2024.08.013 |
| Publisher version: | https://doi.org/10.1016/j.cub.2024.08.013 |
| Language: | English |
| Additional information: | Copyright © 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Actin; WAVE regulatory complex; WRC; Arp2/3; Scar/WAVE; polyproline; N-WASP; lamellipodium; VCA domain; Dictyostelium discoideum |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10204580 |
Loading...
Loading...Loading...| 1. |  United Kingdom | 2 |
| 2. |  United States | 1 |
| 3. |  Netherlands | 1 |
| 4. |  Russian Federation | 1 |
Archive Staff Only
 |
View Item |
