학술논문

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity.
Document Type
article
Source
PLoS biology. 17(10)
Subject
HL-60 Cells
Cell Membrane
Pseudopodia
Humans
Actins
N-Formylmethionine Leucyl-Phenylalanine
Chemotactic Factors
Microscopy
Atomic Force
Cell Adhesion
Signal Transduction
Chemotaxis
Cell Polarity
Gene Expression Regulation
Surface Properties
Wiskott-Aldrich Syndrome Protein Family
Actin-Related Protein 2-3 Complex
HEK293 Cells
Biomechanical Phenomena
CRISPR-Cas Systems
Gene Editing
Microscopy
Atomic Force
1.1 Normal biological development and functioning
Generic Health Relevance
Developmental Biology
Biological Sciences
Medical and Health Sciences
Agricultural and Veterinary Sciences
Language
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.