A mechanism of leading-edge protrusion in the absence of Arp2/3 complex

Praveen Suraneni, Ben Fogelson, Boris Rubinstein, Philippe Noguera, Niels Volkmann, Dorit Hanein, Alex Mogilner, Rong Li

Research output: Contribution to journalArticle

Abstract

Cells employ protrusive leading edges to navigate and promote their migration in diverse physiological environments. Classical models of leading-edge protrusion rely on a treadmilling dendritic actin network that undergoes continuous assembly nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Recent work demonstrated, however, that, in the absence of the Arp2/3 complex, fibroblast cells adopt a leading edge with filopodia-like protrusions (FLPs) and maintain an ability to move, albeit with altered responses to different environmental signals. We show that formin-family actin nucleators are required for the extension of FLPs but are insufficient to produce a continuous leading edge in fibroblasts lacking Arp2/3 complex. Myosin II is concentrated in arc-like regions of the leading edge in between FLPs, and its activity is required for coordinated advancement of these regions with formin-generated FLPs. We propose that actomyosin contraction acting against membrane tension advances the web of arcs between FLPs. Predictions of this model are verified experimentally. The dependence of myosin II in leading-edge advancement helps explain the previously reported defect in directional movement in the Arpc3-null fibroblasts. We provide further evidence that this defect is cell autonomous during chemotaxis.

Original languageEnglish (US)
Pages (from-to)901-912
Number of pages12
JournalMolecular Biology of the Cell
Volume26
Issue number5
DOIs
StatePublished - Mar 1 2015

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Actin-Related Protein 2-3 Complex
Pseudopodia
Myosin Type II
Fibroblasts
Actins
Actomyosin
Aptitude
Chemotaxis
Membranes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Suraneni, P., Fogelson, B., Rubinstein, B., Noguera, P., Volkmann, N., Hanein, D., ... Li, R. (2015). A mechanism of leading-edge protrusion in the absence of Arp2/3 complex. Molecular Biology of the Cell, 26(5), 901-912. https://doi.org/10.1091/mbc.E14-07-1250

A mechanism of leading-edge protrusion in the absence of Arp2/3 complex. / Suraneni, Praveen; Fogelson, Ben; Rubinstein, Boris; Noguera, Philippe; Volkmann, Niels; Hanein, Dorit; Mogilner, Alex; Li, Rong.

In: Molecular Biology of the Cell, Vol. 26, No. 5, 01.03.2015, p. 901-912.

Research output: Contribution to journalArticle

Suraneni, P, Fogelson, B, Rubinstein, B, Noguera, P, Volkmann, N, Hanein, D, Mogilner, A & Li, R 2015, 'A mechanism of leading-edge protrusion in the absence of Arp2/3 complex', Molecular Biology of the Cell, vol. 26, no. 5, pp. 901-912. https://doi.org/10.1091/mbc.E14-07-1250
Suraneni P, Fogelson B, Rubinstein B, Noguera P, Volkmann N, Hanein D et al. A mechanism of leading-edge protrusion in the absence of Arp2/3 complex. Molecular Biology of the Cell. 2015 Mar 1;26(5):901-912. https://doi.org/10.1091/mbc.E14-07-1250
Suraneni, Praveen ; Fogelson, Ben ; Rubinstein, Boris ; Noguera, Philippe ; Volkmann, Niels ; Hanein, Dorit ; Mogilner, Alex ; Li, Rong. / A mechanism of leading-edge protrusion in the absence of Arp2/3 complex. In: Molecular Biology of the Cell. 2015 ; Vol. 26, No. 5. pp. 901-912.
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