title: Transient assembly of F-actin by phagosomes delays phagosome fusion with lysosomes in cargo-overloaded macrophages.
abstract: Dynamic remodelling of the cortical actin cytoskeleton is required for phagocytic uptake of pathogens and other particles by macrophages. Actin can also be nucleated de novo on membranes of nascent phagosomes, a process that can stimulate or inhibit phagosome fusion with lysosomes. Recently, phagosomes were shown to polymerize actin in transient pulses, called actin ;flashing', whose function remains unexplained. Here, we investigated phagosomal actin dynamics in live macrophages expressing actin tagged with green fluorescent protein (GFP). We show that only immature phagosomes can transiently induce assembly of actin coat, which forms a barrier preventing phagosome-lysosome docking and fusion. The capacity of phagosomes to assemble actin is enhanced in cells exposed to increased phagocytic load, which also exhibit a delay in phagosome maturation. Parallel analysis indicated that polymerization of actin on macropinosomes also induces compression and propulsion. We show that dynamic interactions between membrane elastic tension and compression forces of polymerizing actin can also lead to macropinosome constriction and scission - a process that is obstructed on rigid phagosomes. We hypothesize that the rate of individual phagosome maturation, as well as the biogenesis and remodelling of macropinosomes, can be regulated by the extent and manner of actin assembly on their membrane.
authors.affiliation: Cell Biology and Biophysics Unit, EMBL Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany. liebl@embl.de
authors.forename: David
authors.initials: D
authors.lastname: Liebl
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D015536:Down-Regulation; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008561:Membrane Fusion; D051379:Mice; D008954:Models, Biological; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000199:Actins