Lamellipodia-like actin networks in cells lacking WAVE regulatory complex

Author:

Kage Frieda12,Döring Hermann12,Mietkowska Magdalena12,Schaks Matthias12,Grüner Franziska12,Stahnke Stephanie2,Steffen Anika2,Müsken Mathias23,Stradal Theresia E. B.2,Rottner Klemens124ORCID

Affiliation:

1. Zoological Institute, Technische Universität Braunschweig 1 Division of Molecular Cell Biology , , Spielmannstrasse 7, 38106 Braunschweig , Germany

2. Helmholtz Centre for Infection Research 2 Department of Cell Biology , , Inhoffenstrasse 7, 38124 Braunschweig , Germany

3. Helmholtz Centre for Infection Research 3 Central Facility for Microscopy , , 38124 Braunschweig , Germany

4. Braunschweig Integrated Centre of Systems Biology (BRICS) 4 , 38106 Braunschweig , Germany

Abstract

ABSTRACT Cell migration frequently involves the formation of lamellipodia induced by Rac GTPases activating WAVE regulatory complex (WRC) to drive Arp2/3 complex-dependent actin assembly. Previous genome editing studies in B16-F1 melanoma cells solidified the view of an essential, linear pathway employing the aforementioned components. Here, disruption of the WRC subunit Nap1 (encoded by Nckap1) and its paralog Hem1 (encoded by Nckap1l) followed by serum and growth factor stimulation, or active GTPase expression, revealed a pathway to formation of Arp2/3 complex-dependent lamellipodia-like structures (LLS) that requires both Rac and Cdc42 GTPases, but not WRC. These phenotypes were independent of the WRC subunit eliminated and coincided with the lack of recruitment of Ena/VASP family actin polymerases. Moreover, aside from Ena/VASP proteins, LLS contained all lamellipodial regulators tested, including cortactin (also known as CTTN), the Ena/VASP ligand lamellipodin (also known as RAPH1) and FMNL subfamily formins. Rac-dependent but WRC-independent actin remodeling could also be triggered in NIH 3T3 fibroblasts by growth factor (HGF) treatment or by gram-positive Listeria monocytogenes usurping HGF receptor signaling for host cell invasion. Taken together, our studies thus establish the existence of a signaling axis to Arp2/3 complex-dependent actin remodeling at the cell periphery that operates without WRC and Ena/VASP.

Publisher

The Company of Biologists

Subject

Cell Biology

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