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...
Main Authors: | , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2019-10-01
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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. |
first_indexed | 2024-12-17T09:59:56Z |
format | Article |
id | doaj.art-3f153d5d621647d69fdf25c9aa2954fd |
institution | Directory Open Access Journal |
issn | 1544-9173 1545-7885 |
language | English |
last_indexed | 2024-12-17T09:59:56Z |
publishDate | 2019-10-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Biology |
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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