Abstract

Initiation of Lamellipodia and Ruffles Involves Cooperation Between mDia1 and the Arp2/3 Complex

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.

Topics & Tags

Read full article:

Isogai T, van der Kammen R, Leyton-Puig D, Kedziora KM, Jalink K, Innocenti M:
Initiation of Lamellipodia and Ruffles Involves Cooperation Between mDia1 and the Arp2/3 Complex

Interested to know more?

Talk to our experts. We are happy to answer all your questions and concerns.

Contact Us

Do you prefer personal consulting?

  • Leica Microsystems Inc.
    1700 Leider Lane
    Buffalo Grove, IL 60089 United States
    Office Phone : +1 800 248 0123
    Service Phone : 1 800 248 0223
    Fax : +1 847-236-3009

You will find a more detailed list of local contacts here.