Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis

eLife

Daan Vorselen¹  Julie A Theriot¹  Mira Krendel²  Sarah R Barger²  Yifan Wang³  Wei Cai³  Nils C Gauthier⁴ 

[1] Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, United States;Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, United States;Department of Mechanical Engineering, Stanford University, Stanford, United States;IFOM, FIRC Institute of Molecular Oncology, Milan, Italy;

关键词: phagocytosis;    cytoskeleton;    actin;    myosin;   

DOI  :  10.7554/eLife.68627

来源: DOAJ

【 摘 要 】

Phagocytosis requires rapid actin reorganization and spatially controlled force generation to ingest targets ranging from pathogens to apoptotic cells. How actomyosin activity directs membrane extensions to engulf such diverse targets remains unclear. Here, we combine lattice light-sheet microscopy (LLSM) with microparticle traction force microscopy (MP-TFM) to quantify actin dynamics and subcellular forces during macrophage phagocytosis. We show that spatially localized forces leading to target constriction are prominent during phagocytosis of antibody-opsonized targets. This constriction is largely driven by Arp2/3-mediated assembly of discrete actin protrusions containing myosin 1e and 1f (‘teeth’) that appear to be interconnected in a ring-like organization. Contractile myosin-II activity contributes to late-stage phagocytic force generation and progression, supporting a specific role in phagocytic cup closure. Observations of partial target eating attempts and sudden target release via a popping mechanism suggest that constriction may be critical for resolving complex in vivo target encounters. Overall, our findings present a phagocytic cup shaping mechanism that is distinct from cytoskeletal remodeling in 2D cell motility and may contribute to mechanosensing and phagocytic plasticity.

【 授权许可】

Unknown