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.

Isogai, T., van der Kammen, R., Leyton-Puig, D., Kedziora, K., Jalink, K., Innocenti, M. (2015). Initiation of lamellipodia and ruffles involves cooperation between mDia1 and the Arp2/3 complex. JOURNAL OF CELL SCIENCE, 128(20), 3796-3810 [10.1242/jcs.176768].

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

Innocenti M
2015

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.
Articolo in rivista - Articolo scientifico
Actin; Arp2/3; Cell migration; Lamellipodia; MDia1; Ruffles;
English
2015
128
20
3796
3810
open
Isogai, T., van der Kammen, R., Leyton-Puig, D., Kedziora, K., Jalink, K., Innocenti, M. (2015). Initiation of lamellipodia and ruffles involves cooperation between mDia1 and the Arp2/3 complex. JOURNAL OF CELL SCIENCE, 128(20), 3796-3810 [10.1242/jcs.176768].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/396112
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