Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

PLoS Biol. 2019 Oct 10;17(10):e3000457. doi: 10.1371/journal.pbio.3000457. eCollection 2019 Oct.


Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted actin-related protein 2/3 (Arp2/3) and the WASP-family verprolin homologous protein (WAVE) complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / genetics*
  • Actins / metabolism
  • Biomechanical Phenomena
  • CRISPR-Cas Systems
  • Cell Adhesion / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Cell Polarity / drug effects
  • Cell Polarity / genetics*
  • Chemotactic Factors / pharmacology
  • Chemotaxis / drug effects
  • Chemotaxis / genetics*
  • Gene Editing
  • Gene Expression Regulation
  • HEK293 Cells
  • HL-60 Cells
  • Humans
  • Microscopy, Atomic Force
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Pseudopodia / ultrastructure
  • Signal Transduction
  • Surface Properties
  • Wiskott-Aldrich Syndrome Protein Family / deficiency
  • Wiskott-Aldrich Syndrome Protein Family / genetics*


  • Actin-Related Protein 2-3 Complex
  • Actins
  • Chemotactic Factors
  • WASF1 protein, human
  • Wiskott-Aldrich Syndrome Protein Family
  • N-Formylmethionine Leucyl-Phenylalanine