Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells.
Trypanosoma cruzi invades most nucleated cells by a mechanism distinct from classical phagocytosis. Although parasites enter at the lysosome-poor peripheral cell margins, lysosomal markers are immediately incorporated into the parasitophorous vacuole. No accumulation of polymerized actin was detected around recently internalized parasites, and disruption of microfilaments significantly facilitated invasion. Lysosomes were observed to aggregate at the sites of trypanosome attachment and to fuse with the vacuole at early stages of its formation. Experimentally induced, microtubule-dependent movement of lysosomes from the perinuclear area to the cell periphery enhanced entry. Conditions that deplete cells of peripheral lysosomes or interfere with lysosomal fusion capacity inhibited invasion. These observations reveal a novel mechanism for cell invasion:recruitment of lysosomes for fusion at the site of parasite internalization.
Tardieux
I
I
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Webster
P
P
Ravesloot
J
J
Boron
W
W
Lunn
J A
JA
Heuser
J E
JE
Andrews
N W
NW
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000469:parasitology*; D006790:Host-Parasite Interactions; D008247:Lysosomes / Q000469:parasitology*; D008870:Microtubules / Q000502:physiology; D051381:Rats; D015398:Signal Transduction; D013395:Sucrose / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000502:physiology*; D014617:Vacuoles / Q000469:parasitology
D013395:Sucrose