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

Tadamoto Isogai1, Rob van der Kammen1, Daniela Leyton-Puig2

  • 1Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.

Journal of Cell Science
|September 10, 2015
PubMed

Insights

The study reveals that mDia1 and the Arp2/3 complex cooperate to initiate cell membrane protrusions like lamellipodia and ruffles, crucial for cell migration.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Actin polymerization by the Arp2/3 complex drives lamellipodia and ruffle formation.
  • The precise mechanisms initiating these membrane protrusions remain unclear.
  • Understanding these processes is key to cell migration research.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the initiation of lamellipodia and ruffles.
  • To investigate the role of mDia1 in actin dynamics and cell protrusion.
  • To determine how mDia1 interacts with the Arp2/3 complex in regulating cell migration.

Main Methods:

  • Knockdown and rescue experiments to assess mDia1 function.
  • Biochemical assays to analyze actin filament polymerization.
  • Optogenetics and functional complementation to study protein interactions.
  • Genetic and pharmacological interference to evaluate cellular processes.

Main Results:

  • mDia1 acts as an epidermal growth factor (EGF)-regulated actin nucleator involved in membrane ruffling.
  • mDia1 polymerizes linear actin filaments, which activates the Arp2/3 complex.
  • mDia1 and Arp2/3 complex cooperate sequentially to initiate lamellipodia and ruffles.
  • Disruption of this cooperation impairs cell ruffling and migration.

Conclusions:

  • The lamellipodium and ruffle initiation machinery involves sequential action of two actin nucleators: mDia1 and Arp2/3 complex.
  • This coordinated mechanism regulates membrane protrusion and is essential for cell migration.
  • The findings provide new insights into the regulation of cell motility.
Keywords:
ActinArp2/3Cell migrationLamellipodiaRufflesmDia1

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