Surface-targeted lysosomal membrane glycoprotein-1 (Lamp-1) enhances lysosome exocytosis and cell invasion by Trypanosoma cruzi

To gain entry into non-phagocytic cells, Trypanosoma cruzi trypomastigotes recruit lysosomes to the host cell surface. Lysosome fusion at the site of parasite entry leads to the formation of a parasitophorous vacuole with lys osomal properties. Here, we show that increased expression of the lysosomal membrane glycoprotein Lamp-1 at the cell surface renders CHO cells more su sceptible to trypomastigote invasion in a microtubule-dependent fashion. Mu tation of critical residues in the lysosome-targeting motif of Lamp-1 aboli shed the enhancement of T. cruzi invasion. This suggests that interactions dependent on Lamp-1 cytoplasmic tail motifs, and not the surface-exposed lu minal domain, modulate T. cruzi entry. Measurements of Ca2+-triggered exocy tosis of lysosomes in these cell lines revealed an enhancement of beta -hex osaminidase release in cells expressing wild-type Lamp-1 on the plasma memb rane; this effect was not observed in cell lines transfected with Lamp-1 cy toplasmic tail mutants. These results also implicate Ca2+-regulated lysosom e exocytosis in cell invasion by T. cruzi and indicate a role for the Lamp- 1 cytosolic domain in promoting more efficient fusion of lysosomes with the plasma membrane.