WASP family proteins and formins compete in pseudopod- and bleb-based migration

Davidson, A. J., Amato, C., Thomason, P. A. and Insall, R. H. (2018) WASP family proteins and formins compete in pseudopod- and bleb-based migration. Journal of Cell Biology, 217(2), pp. 701-714. (doi: 10.1083/jcb.201705160) (PMID:29191847) (PMCID:PMC5800805)

Abstract

Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration.

• Item Type: Articles
• Keywords: Cell biology.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Thomason, Dr Peter and Davidson, Mr Andrew and Insall, Professor Robert and Amato, Clelia
• Authors: Davidson, A. J., Amato, C., Thomason, P. A., and Insall, R. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Cell Biology
• Publisher: Rockefeller University Press
• ISSN: 0021-9525
• ISSN (Online): 1540-8140
• Published Online: 30 November 2017
• Copyright Holders: Copyright © 2018 Davidson et al.
• First Published: First published in Journal of Cell Biology 217(2):701-714
• Publisher Policy: Reproduced under a Creative Commons License