Actin-Membrane Release Initiates Cell Protrusions

Erik S. Welf, Christopher E. Miles, Jaewon Huh, Etai Sapoznik, Joseph Chi, Meghan K. Driscoll, Tadamoto Isogai, Jungsik Noh, Andrew D. Weems, Theresa Pohlkamp, Kevin Dean, Reto Fiolka, Alex Mogilner, Gaudenz Danuser

Research output: Contribution to journalArticlepeer-review


Despite the well-established role of actin polymerization as a driving mechanism for cell protrusion, upregulated actin polymerization alone does not initiate protrusions. Using a combination of theoretical modeling and quantitative live-cell imaging experiments, we show that local depletion of actin-membrane links is needed for protrusion initiation. Specifically, we show that the actin-membrane linker ezrin is depleted prior to protrusion onset and that perturbation of ezrin's affinity for actin modulates protrusion frequency and efficiency. We also show how actin-membrane release works in concert with actin polymerization, leading to a comprehensive model for actin-driven shape changes. Actin-membrane release plays a similar role in protrusions driven by intracellular pressure. Thus, our findings suggest that protrusion initiation might be governed by a universal regulatory mechanism, whereas the mechanism of force generation determines the shape and expansion properties of the protrusion.

Original languageEnglish (US)
Pages (from-to)723-736.e8
JournalDevelopmental Cell
Issue number6
StatePublished - Dec 21 2020


  • Brownian ratchet model
  • actin dynamics
  • cytoskeleton
  • intracellular force
  • lamellipodium
  • morphology
  • polymerization
  • protrusion
  • shape change
  • Cell Surface Extensions/metabolism
  • Actins/metabolism
  • Humans
  • Cells, Cultured
  • Stress, Mechanical
  • Male
  • Cytoskeletal Proteins/metabolism
  • Animals
  • Cell Membrane/metabolism
  • Cell Line, Tumor
  • Cytoskeleton/metabolism
  • Female
  • Mice

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • Cell Biology
  • Developmental Biology


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