Open AccessF-actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages
Author(s) -
Mathieu B. Poirier,
Cara Fiorino,
Thiviya K. Rajasekar,
Rene E. Harrison
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.239384
Subject(s) - phagosome , biology , actin , microbiology and biotechnology , myosin , filopodia , cytoskeleton , phagocytosis , biophysics , biochemistry , cell
The mechanism and role of transient F-actin recruitment or F-actin “flashes” on phagosomes remains enigmatic. Here we provide a comprehensive characterization of F-actin flashing dynamics on phagosomes including receptor and signaling involvement. F-actin flashes predominate during the integrin-driven CR-mediated phagocytosis. F-actin flashes begin shortly after internalization and persist on phagosomes for ∼3 minutes before disassembling and reassembling several times within the first hour. Strikingly, the appearance of F-actin flashes on phagosomes coincides with RBC morphological deformation, lysis and occasional fission events. The cadence of flashes depends on particle stiffness and the F-actin networks on phagosomes are enriched in mechanosensitive components including focal adhesion proteins, RhoA and actomyosin. Inhibiting Arp2/3 and myosin IIA activity significantly reduces the frequency at which phagosome cargo becomes deformed during transient F-actin accumulation. At later time points, post-F-actin flashing, an enhanced degradation of phagosome contents is observed, compared to non-flashing phagosomes. Together these data suggest that actomyosin-driven phagosome contractions serve to physically disrupt malleable particles, a process akin to mastication, to enhance later enzymatic digestion.