Brian R. Graziano (Author), Jason P. Town (Author), Ewa Sitarska (Author), Tamas L. Nagy (Author), Miha Fošnarič (Author), Samo Penič (Author), Aleš Iglič (Author), Veronika Kralj-Iglič (Author), Nir S. Gov (Author), Alba Diz-Muñoz (Author), Orion D. Weiner (Author)

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.

Keywords

branched actin networks;neutrophil polarity;neutrophil motility;adherent conditions;membrane tension;cell confinement;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL ZF - University College of Health Studies
UDC: 577
COBISS: 5728875 Link will open in a new window
ISSN: 1545-7885
Views: 708
Downloads: 440
Average score: 0 (0 votes)
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Other data

Type (COBISS): Article
Pages: str. 1-34
Volume: ǂVol. ǂ17
Issue: ǂiss. ǂ10
Chronology: 2019
DOI: 10.1371/journal.pbio.3000457
ID: 11324698