RT Journal Article
SR Electronic
T1 F-actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP jcs239384
DO 10.1242/jcs.239384
VO 133
IS 12
A1 Poirier, Mathieu B.
A1 Fiorino, Cara
A1 Rajasekar, Thiviya K.
A1 Harrison, Rene E.
YR 2020
UL http://jcs.biologists.org/content/133/12/jcs239384.abstract
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.