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

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) co...

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Main Authors: Brian R Graziano, Jason P Town, Ewa Sitarska, Tamas L Nagy, Miha Fošnarič, Samo Penič, Aleš Iglič, Veronika Kralj-Iglič, Nir S Gov, Alba Diz-Muñoz, Orion D Weiner
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-10-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3000457
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author Brian R Graziano
Jason P Town
Ewa Sitarska
Tamas L Nagy
Miha Fošnarič
Samo Penič
Aleš Iglič
Veronika Kralj-Iglič
Nir S Gov
Alba Diz-Muñoz
Orion D Weiner
author_facet Brian R Graziano
Jason P Town
Ewa Sitarska
Tamas L Nagy
Miha Fošnarič
Samo Penič
Aleš Iglič
Veronika Kralj-Iglič
Nir S Gov
Alba Diz-Muñoz
Orion D Weiner
author_sort Brian R Graziano
collection DOAJ
description 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.
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spelling doaj.art-3f153d5d621647d69fdf25c9aa2954fd2022-12-21T21:53:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-10-011710e300045710.1371/journal.pbio.3000457Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.Brian R GrazianoJason P TownEwa SitarskaTamas L NagyMiha FošnaričSamo PeničAleš IgličVeronika Kralj-IgličNir S GovAlba Diz-MuñozOrion D WeinerMigratory 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.https://doi.org/10.1371/journal.pbio.3000457
spellingShingle Brian R Graziano
Jason P Town
Ewa Sitarska
Tamas L Nagy
Miha Fošnarič
Samo Penič
Aleš Iglič
Veronika Kralj-Iglič
Nir S Gov
Alba Diz-Muñoz
Orion D Weiner
Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
PLoS Biology
title Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
title_full Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
title_fullStr Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
title_full_unstemmed Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
title_short Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
title_sort cell confinement reveals a branched actin independent circuit for neutrophil polarity
url https://doi.org/10.1371/journal.pbio.3000457
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