Initiation of lamellipodia and ruffles involves cooperation between mDia1 and the Arp2/3 complex

Tadamoto Isogai, Rob van der Kammen, Daniela Leyton-Puig, Katarzyna M. Kedziora, Kees Jalink, Metello Innocenti

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Protrusion of lamellipodia and ruffles requires polymerization of branched actin filaments by the Arp2/3 complex. Although regulation of Arp2/3 complex activity has been extensively investigated, the mechanism of initiation of lamellipodia and ruffles remains poorly understood. Here, we show that mDia1 acts in concert with the Arp2/3 complex to promote initiation of lamellipodia and ruffles. We find that mDia1 is an epidermal growth factor (EGF)-regulated actin nucleator involved in membrane ruffling using a combination of knockdown and rescue experiments. At the molecular level, mDia1 polymerizes linear actin filaments, activating the Arp2/3 complex, and localizes within nascent and mature membrane ruffles. We employ functional complementation experiments and optogenetics to show that mDia1 cooperates with the Arp2/3 complex in initiating lamellipodia and ruffles. Finally, we show that genetic and pharmacological interference with this cooperation hampers ruffling and cell migration. Thus, we propose that the lamellipodium- and ruffle-initiating machinery consists of two actin nucleators that act sequentially to regulate membrane protrusion and cell migration.

Original languageEnglish (US)
Pages (from-to)3796-3810
Number of pages15
JournalJournal of cell science
Volume128
Issue number20
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Actin
  • Arp2/3
  • Cell migration
  • Lamellipodia
  • MDia1
  • Ruffles

ASJC Scopus subject areas

  • Cell Biology

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