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Cell confinement reveals a branched-actin independent circuit for neutrophil polarity
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Cell confinement reveals a branched-actin independent circuit for neutrophil polarity
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Cell confinement reveals a branched-actin independent circuit for neutrophil polarity
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Paper
Cell confinement reveals a branched-actin independent circuit for neutrophil polarity
2019
Overview
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 Arp2/3 and 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. Footnotes * Figs 5D, 6A, 6G-H, and S4 are new. Videos 12-16 are new. Significant reorganization of original data and editing of original text to improve clarity.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
