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

Brian R. Graziano, Jason P. Town, Ewa Sitarska, Tamas L. Nagy, Miha Fosnaric, Samo Penic, Ales Iglic, Veronika Kralj-Iglic, Nir S. Gov, Alba Diz-Munoz, Orion D. Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere3000457
Number of pages34
JournalPLoS Biology
Volume17
Issue number10
DOIs
StatePublished - 10 Oct 2019

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Neuroscience
  • General Agricultural and Biological Sciences

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