Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

• Published in: PLoS biology Vol. 17; no. 10; p. e3000457
• Main Authors: Graziano, Brian R, Town, Jason P, Sitarska, Ewa, Nagy, Tamas L, Fošnarič, Miha, Penič, Samo, Iglič, Aleš, Kralj-Iglič, Veronika, Gov, Nir S, Diz-Muñoz, Alba, Weiner, Orion D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-10-2019; Public Library of Science (PLoS)
• Subjects: Actin; Actin-related protein 2; Actin-Related Protein 2-3 Complex - genetics; Actin-Related Protein 2-3 Complex - metabolism; actins; Actins - genetics; Actins - metabolism; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biology and Life Sciences; Biomechanical Phenomena; Biophysics; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane - ultrastructure; cell membranes; Cell migration; cell polarity; Cell Polarity - drug effects; Cell Polarity - genetics; Chemotactic Factors - pharmacology; Chemotaxis - drug effects; Chemotaxis - genetics; Circuits; Confinement; CRISPR-Cas Systems; Electrical engineering; Engineering and Technology; Experiments; Feedback; Funding; Gene Editing; Gene Expression Regulation; HEK293 Cells; HL-60 Cells; Homology; Humans; hypotonic; Laboratories; Leukocytes (neutrophilic); Medicine and Health Sciences; membrane proteins; membrane structures; Membranes; Microenvironments; Microscopy; Microscopy, Atomic Force; Molecular biology; Molecular modelling; Motility; Muscle proteins; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils; Physical Sciences; Physics; Plasma; Polarity; Polymerization; Proteins; Pseudopodia - drug effects; Pseudopodia - metabolism; Pseudopodia - ultrastructure; Signal Transduction; Software; Stress analysis; Surface Properties; Wiskott-Aldrich Syndrome Protein Family - deficiency; Wiskott-Aldrich Syndrome Protein Family - genetics; Massachusetts; San Francisco California; California; Slovenia; United States > US; Germany
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000457

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.