Dimchev, Georgi AIST Austria; Amiri, Behnam; Humphries, Ashley C.; Schaks, Matthias; Dimchev, Vanessa; Stradal, Theresia E. B.; Faix, Jan; Krause, Matthias; Way, Michael; Falcke, Martin; Rottner, Klemens
Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin-binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex, an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.This article has an associated First Person interview with the first author of the paper.
Journal of Cell Science
This work was supported in part by Deutsche Forschungsgemeinschaft (DFG)[GRK2223/1, RO2414/5-1 (to K.R.), FA350/11-1 (to M.F.) and FA330/11-1 (to J.F.)],as well as by intramural funding from the Helmholtz Association (to T.E.B.S. andK.R.). G.D. was additionally funded by the Austrian Science Fund (FWF) LiseMeitner Program [M-2495]. A.C.H. and M.W. are supported by the Francis CrickInstitute, which receives its core funding from Cancer Research UK [FC001209], theMedical Research Council [FC001209] and the Wellcome Trust [FC001209]. M.K. issupported by the Biotechnology and Biological Sciences Research Council [BB/F011431/1, BB/J000590/1, BB/N000226/1]. Deposited in PMC for release after 6months.
Dimchev GA, Amiri B, Humphries AC, et al. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. 2020;133(7). doi:10.1242/jcs.239020
Dimchev, G. A., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal, T. E. B., … Rottner, K. (2020). Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science, 133(7). https://doi.org/10.1242/jcs.239020
Dimchev, Georgi A, Behnam Amiri, Ashley C. Humphries, Matthias Schaks, Vanessa Dimchev, Theresia E. B. Stradal, Jan Faix, et al. “Lamellipodin Tunes Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal of Cell Science 133, no. 7 (2020). https://doi.org/10.1242/jcs.239020.
G. A. Dimchev et al., “Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation,” Journal of Cell Science, vol. 133, no. 7, 2020.
Dimchev GA, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix J, Krause M, Way M, Falcke M, Rottner K. 2020. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. 133(7).
Dimchev, Georgi A., et al. “Lamellipodin Tunes Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal of Cell Science, vol. 133, no. 7, jcs239020, The Company of Biologists, 2020, doi:10.1242/jcs.239020.
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