PT  - JOURNAL ARTICLE
AU  - Poirier, Mathieu B.
AU  - Fiorino, Cara
AU  - Rajasekar, Thiviya K.
AU  - Harrison, Rene E.
TI  - F-actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages
AID  - 10.1242/jcs.239384
DP  - 2020 Jun 15
TA  - Journal of Cell Science
PG  - jcs239384
VI  - 133
IP  - 12
4099  - http://jcs.biologists.org/content/133/12/jcs239384.short
4100  - http://jcs.biologists.org/content/133/12/jcs239384.full
SO  - J. Cell Sci.2020 Jun 15; 133
AB  - 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 complement receptor (CR)-mediated phagocytosis. F-actin flashes begin shortly after internalization and persist on phagosomes for approximately 3 minutes before disassembling and reassembling several times within the first hour. Strikingly, the appearance of F-actin flashes on phagosomes coincides with morphological deformation, lysis and occasional fission of internalized red blood cells. 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, enhanced degradation of phagosome contents is observed, compared with non-flashing phagosomes. Taken together, these data suggest that actomyosin-driven phagosome contractions serve to disrupt malleable particles physically, a process akin to mastication, to enhance later enzymatic digestion.