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Cell confinement reveals a branched-actin independent circuit for neutrophil polarity
Graziano, Brian R. (Author), Town, Jason P. (Author), Sitarska, Ewa (Author), Nagy, Tamas L. (Author), Fošnarič, Miha (Author), Penič, Samo (Author), Iglič, Aleš (Author), Kralj-Iglič, Veronika (Author), Gov, Nir S. (Author), Diz-Muñoz, Alba (Author), Weiner, Orion D. (Author)

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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.

Language:English
Keywords:branched actin networks, neutrophil polarity, neutrophil motility, adherent conditions, membrane tension, cell confinement
Work type:Article (dk_c)
Tipology:1.01 - Original Scientific Article
Organization:ZF - University College of Health Studies
Year:2019
Number of pages:Str. 1-34
Numbering:Vol. 17, iss. 10
UDC:577
ISSN on article:1545-7885
DOI:10.1371/journal. pbio.3000457 This link opens in a new window
COBISS.SI-ID:5728875 This link opens in a new window
Views:395
Downloads:319
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Record is a part of a journal

Title:PLoS biology
Shortened title:PLoS biol.
Publisher:Public Library of Science
ISSN:1545-7885
COBISS.SI-ID:2943764 This link opens in a new window

Document is financed by a project

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J1-6728
Name:Vpliv anorganskih nanodelcev na biološke membrane

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J2-8166
Name:Anizotropni magnetni nanodelci za magneto-mehansko zdravljenje raka

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J2-8169
Name:Piezoelektrični biomateriali za regeneracijo s pomočjo elektro-stimulacije

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J1-9162
Name:Neurotoksičnost ali neuroprotektivnost nanomatrialov: vpliv biokorone

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:P3-0388
Name:Mehanizmi varovanja zdravja

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:P2-0232
Name:Funkcije in tehnologije kompleksnih sistemov

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:08.12.2019

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