Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 33, Issue 14, Pages -Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E22-06-0210
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Funding
- American Heart Association [18PRE34070066]
- National Institute of General Medical Sciences of the National Institutes of Health [R01GM-138652]
- Italian Association for Cancer Research (AIRC) [20716]
- Howard Hughes Medical Institute
- Cancer Research Institute
- Gordon and Betty Moore Foundation
- HHMI
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This study investigates the phagocytosis of primary bone marrow-derived macrophages using high-resolution imaging and novel biophysical approaches. It is found that the behavior of primary cells during phagocytosis is distinct from immortalized cell lines, exhibiting gentle target constriction and modest polarization of F-actin distribution. Long-tailed myosins 1e/f play a critical role in this process, as deficiency of myo1e/f causes significant changes in F-actin localization. Surprisingly, these changes can be almost fully reversed by inhibiting another myosin motor protein, 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 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.
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