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

Jamie A. Whitelaw*, Karthic Swaminathan, Frieda Kage, Laura M. Machesky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
4 Downloads (Pure)

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.
Original languageEnglish
Article number1635
Number of pages22
JournalCells
Volume9
Issue number7
DOIs
Publication statusPublished - 7 Jul 2020
Externally publishedYes

Keywords

  • actin cytoskeleton
  • WAVE complex
  • stress fibers
  • focal adhesions
  • migration

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