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F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II
Phagocytosis requires rapid remodeling of the actin cytoskeleton for extension of membrane protrusions and force generation to ultimately drive the engulfment of targets. The detailed mechanisms of phagocytosis have almost exclusively been studied in immortalized cell lines. Here, we make use of hig...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727803/ https://www.ncbi.nlm.nih.gov/pubmed/36129777 http://dx.doi.org/10.1091/mbc.E22-06-0210 |
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author | Barger, Sarah R. Vorselen, Daan Gauthier, Nils C. Theriot, Julie A. Krendel, Mira |
author_facet | Barger, Sarah R. Vorselen, Daan Gauthier, Nils C. Theriot, Julie A. Krendel, Mira |
author_sort | Barger, Sarah R. |
collection | PubMed |
description | Phagocytosis requires rapid remodeling of the actin cytoskeleton for extension of membrane protrusions and force generation to ultimately drive the engulfment of targets. The detailed mechanisms of phagocytosis have almost exclusively been studied in immortalized cell lines. Here, we make use of high-resolution imaging and novel biophysical approaches to determine the structural and mechanical features of phagocytosis by primary bone marrow–derived macrophages. We find that the signature behavior of these primary cells is distinct from macrophage-like cell lines; specifically, it is gentle, with only weak target constriction and modest polarization of the F-actin distribution inside the phagocytic cup. We show that long-tailed myosins 1e/f are critical for this organization. Deficiency of myo1e/f causes dramatic shifts in F-actin localization, reducing F-actin at the phagocytic cup base and enhancing F-actin–mediated constriction at the cup rim. Surprisingly, these changes can be almost fully reverted upon inhibition of another myosin motor protein, myosin-II. Hence, we show that the biomechanics and large-scale organization of phagocytic cups is tightly regulated through competing contributions from myosin-Ie/f and myosin-II. |
format | Online Article Text |
id | pubmed-9727803 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-97278032023-02-02 F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II Barger, Sarah R. Vorselen, Daan Gauthier, Nils C. Theriot, Julie A. Krendel, Mira Mol Biol Cell Brief Reports Phagocytosis requires rapid remodeling of the actin cytoskeleton for extension of membrane protrusions and force generation to ultimately drive the engulfment of targets. The detailed mechanisms of phagocytosis have almost exclusively been studied in immortalized cell lines. Here, we make use of high-resolution imaging and novel biophysical approaches to determine the structural and mechanical features of phagocytosis by primary bone marrow–derived macrophages. We find that the signature behavior of these primary cells is distinct from macrophage-like cell lines; specifically, it is gentle, with only weak target constriction and modest polarization of the F-actin distribution inside the phagocytic cup. We show that long-tailed myosins 1e/f are critical for this organization. Deficiency of myo1e/f causes dramatic shifts in F-actin localization, reducing F-actin at the phagocytic cup base and enhancing F-actin–mediated constriction at the cup rim. Surprisingly, these changes can be almost fully reverted upon inhibition of another myosin motor protein, myosin-II. Hence, we show that the biomechanics and large-scale organization of phagocytic cups is tightly regulated through competing contributions from myosin-Ie/f and myosin-II. The American Society for Cell Biology 2022-11-18 /pmc/articles/PMC9727803/ /pubmed/36129777 http://dx.doi.org/10.1091/mbc.E22-06-0210 Text en © 2022 Barger et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License. |
spellingShingle | Brief Reports Barger, Sarah R. Vorselen, Daan Gauthier, Nils C. Theriot, Julie A. Krendel, Mira F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II |
title | F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II |
title_full | F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II |
title_fullStr | F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II |
title_full_unstemmed | F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II |
title_short | F-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-I and myosin-II |
title_sort | f-actin organization and target constriction during primary macrophage phagocytosis is balanced by competing activity of myosin-i and myosin-ii |
topic | Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727803/ https://www.ncbi.nlm.nih.gov/pubmed/36129777 http://dx.doi.org/10.1091/mbc.E22-06-0210 |
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