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Membrane-cytoskeleton mechanical feedback mediated by myosin-I controls phagocytic efficiency

Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, Mark S. Mooseker, Richard A. Flavell, Tatyana Svitkina, Patrick W. Oakes, View ORCID ProfileMira Krendel, View ORCID ProfileNils Gauthier
doi: https://doi.org/10.1101/433631
Sarah R. Barger
1Cell and Developmental Biology Department, State University of New York Upstate Medical University, Syracuse, NY
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Nicholas S. Reilly
2Department of Physics, University of Rochester, Rochester, NY
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Maria S. Shutova
3Department of Biology, University of Pennsylvania, Philadelphia, PA
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Qingsen Li
4IFOM, FIRC Institute of Molecular Oncology, Milan, Italy
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Paolo Maiuri
4IFOM, FIRC Institute of Molecular Oncology, Milan, Italy
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Mark S. Mooseker
5Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT
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Richard A. Flavell
6Department of Immunobiology, Yale University School of Medicine, New Haven, CT
7Howard Hughes Medical Institute, Yale University, New Haven, CT
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Tatyana Svitkina
3Department of Biology, University of Pennsylvania, Philadelphia, PA
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Patrick W. Oakes
2Department of Physics, University of Rochester, Rochester, NY
8Department of Biology, University of Rochester, Rochester, NY
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Mira Krendel
1Cell and Developmental Biology Department, State University of New York Upstate Medical University, Syracuse, NY
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  • ORCID record for Mira Krendel
  • For correspondence: krendelm@upstate.edu nils.gauthier@gmail.com
Nils Gauthier
4IFOM, FIRC Institute of Molecular Oncology, Milan, Italy
9Mechanobiology Institute, MBI, National University of Singapore, Singapore
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  • ORCID record for Nils Gauthier
  • For correspondence: krendelm@upstate.edu nils.gauthier@gmail.com
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Abstract

Phagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.

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Posted October 02, 2018.
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Membrane-cytoskeleton mechanical feedback mediated by myosin-I controls phagocytic efficiency
Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, Mark S. Mooseker, Richard A. Flavell, Tatyana Svitkina, Patrick W. Oakes, Mira Krendel, Nils Gauthier
bioRxiv 433631; doi: https://doi.org/10.1101/433631
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Membrane-cytoskeleton mechanical feedback mediated by myosin-I controls phagocytic efficiency
Sarah R. Barger, Nicholas S. Reilly, Maria S. Shutova, Qingsen Li, Paolo Maiuri, Mark S. Mooseker, Richard A. Flavell, Tatyana Svitkina, Patrick W. Oakes, Mira Krendel, Nils Gauthier
bioRxiv 433631; doi: https://doi.org/10.1101/433631

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