Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation

Dimchev, G.; Amiri, B.; Humphries, A. C.; Schaks, M.; Dimchev, V.; Stradal, T. E. B.; Faix, J.; Krause, M.; Way, M.; Falcke, M.; Rottner, K.

doi:10.1101/777326

bioRxiv · 10.1101/777326

Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation

Dimchev, G.·Amiri, B.·Humphries, A. C.·Schaks, M.·Dimchev, V.·Stradal, T. E. B.·Faix, J.·Krause, M.·Way, M.·Falcke, M.·Rottner, K.

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Abstract

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 (WRC), 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. Summary statementWe describe how genetic ablation of the prominent actin- and VASP-binding protein lamellipodin combined with software-aided protrusion analysis uncovers mechanistic insights into its cellular function during cell migration.

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Dimchev, G., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal, T. E. B., Faix, J., Krause, M., Way, M., Falcke, M., Rottner, K.. 2019-09-20. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. https://doi.org/10.1101/777326

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