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WAVE and Arp2/3 jointly inhibit filopodium formation by entering into a complex with mDia2

Petra Beli1, Debora Mascheroni, Dalu Xu

  • 1Institute of Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.

Nature Cell Biology
|June 3, 2008
PubMed

Insights

WAVE and the Arp2/3 complex coordinate cell protrusions. They promote ruffling and inhibit mDia2-dependent filopodia formation, revealing a key mechanism for actin-based extension control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Lamellipodia/ruffles and filopodia are actin-based cell extensions with distinct structures and functions.
  • Mechanisms coordinating the formation of these diverse actin protrusions remain poorly understood.
  • The roles of WAVE proteins, mDia2, and the Arp2/3 complex in actin dynamics are established but their interplay in protrusion formation is unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which cells coordinate the formation of lamellipodia/ruffles and filopodia.
  • To investigate the interplay between WAVE, mDia2, and the Arp2/3 complex in regulating actin-based plasma membrane protrusions.

Main Methods:

  • Investigated protein interactions using a multimolecular complex assay.
  • Utilized EGF stimulation to induce actin-based protrusions.
  • Employed knockdown strategies for WAVE/Abi1/Nap1/PIR121 (WANP) complex and Arp2/3 complex.
  • Observed effects of WAVE2 reintroduction in knockdown cells.

Main Results:

  • WAVE protein forms a complex with mDia2 and the Arp2/3 complex.
  • EGF-induced ruffling depends on WAVE and Arp2/3 but not mDia2.
  • Filopodia formation is dependent on mDia2 and inversely correlated with its disengagement from WAVE.
  • Loss of WANP or Arp2/3 complex enhances mDia2-dependent filopodia formation.
  • WAVE2 reintroduction suppresses filopodia formation in WANP-knockdown cells.

Conclusions:

  • WAVE and the Arp2/3 complex act in concert to regulate distinct actin-based plasma membrane protrusions.
  • These complexes promote ruffling while simultaneously inhibiting mDia2-induced filopodia formation.
  • This coordinated action provides a novel mechanism for controlling cell shape and motility.

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