Transport Motility of Phagosomes on Actin and Microtubules Regulates Timing and Kinetics of Their Maturation

Abstract

AbstractPhagosome maturation, in which ingested pathogens are degraded through a complex sequence of biochemical changes, is an essential process in infection control and tissue homeostasis. The maturation of phagosomes requires their intracellular transport. However, mechanisms underlying this dynamical-biochemical interdependence is poorly understood due to the lack of methods to independently manipulate either process. Here we present a study to magnetically manipulate the transport of single phagosomes and simultaneously measure their maturation and degradative functions. We reveal that the transport velocity of phagosomes acts as a maturation clock to regulate the timing of biochemical signaling activities in phagosomes. We show that velocity of phagosomes on microtubules determines their rate of fusion with lysosomes and consequently the rate of lumen acidification, following a linear relationship. Meanwhile, the timing of phagosome transport from actin cortex to microtubules controls the kinetics of early phagosome assembly and rate of transition to late phagosomes.