Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis
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...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:aef0f4ad09434fbab2364d8bb7e93e642021-11-24T12:33:37ZPhagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis10.7554/eLife.686272050-084Xe68627https://doaj.org/article/aef0f4ad09434fbab2364d8bb7e93e642021-10-01T00:00:00Zhttps://elifesciences.org/articles/68627https://doaj.org/toc/2050-084XPhagocytosis 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.Daan VorselenSarah R BargerYifan WangWei CaiJulie A TheriotNils C GauthierMira KrendeleLife Sciences Publications LtdarticlephagocytosiscytoskeletonactinmyosinMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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phagocytosis cytoskeleton actin myosin Medicine R Science Q Biology (General) QH301-705.5 |
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phagocytosis cytoskeleton actin myosin Medicine R Science Q Biology (General) QH301-705.5 Daan Vorselen Sarah R Barger Yifan Wang Wei Cai Julie A Theriot Nils C Gauthier Mira Krendel Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis |
description |
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. |
format |
article |
author |
Daan Vorselen Sarah R Barger Yifan Wang Wei Cai Julie A Theriot Nils C Gauthier Mira Krendel |
author_facet |
Daan Vorselen Sarah R Barger Yifan Wang Wei Cai Julie A Theriot Nils C Gauthier Mira Krendel |
author_sort |
Daan Vorselen |
title |
Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis |
title_short |
Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis |
title_full |
Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis |
title_fullStr |
Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis |
title_full_unstemmed |
Phagocytic ‘teeth’ and myosin-II ‘jaw’ power target constriction during phagocytosis |
title_sort |
phagocytic ‘teeth’ and myosin-ii ‘jaw’ power target constriction during phagocytosis |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/aef0f4ad09434fbab2364d8bb7e93e64 |
work_keys_str_mv |
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_version_ |
1718415068276719616 |