The WAVE regulatory complex is required to balance protrusion and adhesion in migration

Whitelaw, J. A., Swaminathan, K., Kage, F. and Machesky, L. M. (2020) The WAVE regulatory complex is required to balance protrusion and adhesion in migration. Cells, 9(7), 1635. (doi: 10.3390/cells9071635) (PMID:32646006) (PMCID:PMC7407199)

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Abstract

Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by the WAVE regulatory complex (WRC). Using inducible Nckap1 floxed mouse embryonic fibroblasts (MEFs), we confirm that the WRC is required for lamellipodia formation, and importantly, for generating the retrograde flow of actin from the leading cell edge. The loss of NCKAP1 also affects cell spreading and focal adhesion dynamics. In the absence of lamellipodium, cells can become elongated and move with a single thin pseudopod, which appears devoid of N-WASP. This phenotype was more prevalent on collagen than fibronectin, where we observed an increase in migratory speed. Thus, 2D cell migration on collagen is less dependent on branched actin.

Item Type:Articles
Additional Information:This research was funded by CRUK Core grant A15673 awarded to L.M.M. F.K. was supported by the Deutsche Forschungsgemeinschaft (grant RO2414/3-2 to Klemens Rottner).
Keywords:Actin cytoskeleton, WAVE complex, stress fibers, focal adhesions, migration.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura
Creator Roles:
Machesky, L. M.Conceptualization, Methodology, Validation, Investigation, Writing – original draft, Writing – review and editing, Supervision, Project administration, Funding acquisition
Authors: Whitelaw, J. A., Swaminathan, K., Kage, F., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cells
Publisher:MDPI
ISSN:2073-4409
ISSN (Online):2073-4409
Published Online:07 July 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cells 9(7): 1635
Publisher Policy:Reproduced under a Creative Commons License

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