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)

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
• Typology: 1.01 - Original Scientific Article
• Organization: ZF - Faculty of Health Sciences
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: Str. 1-34
• Numbering: Vol. 17, iss. 10
• PID: 20.500.12556/RUL-113160
• UDC: 577
• ISSN on article: 1545-7885
• DOI: 10.1371/journal. pbio.3000457
• COBISS.SI-ID: 5728875
• Publication date in RUL: 08.12.2019

Record is a part of a journal

• Title: PLoS biology
• Shortened title: PLoS biol.
• Publisher: PLOS
• ISSN: 1545-7885
• COBISS.SI-ID: 2943764

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