Surface-targeted Lysosomal Membrane glycoprotein-1 (Lamp-1) Enhances Lysosome Exocytosis and Cell Invasion by Trypanosoma Cruzi

Cell Microbiol. 2000 Dec;2(6):477-86. doi: 10.1046/j.1462-5822.2000.00071.x.

Abstract

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 lysosomal properties. Here, we show that increased expression of the lysosomal membrane glycoprotein Lamp-1 at the cell surface renders CHO cells more susceptible to trypomastigote invasion in a microtubule-dependent fashion. Mutation of critical residues in the lysosome-targeting motif of Lamp-1 abolished the enhancement of T. cruzi invasion. This suggests that interactions dependent on Lamp-1 cytoplasmic tail motifs, and not the surface-exposed luminal domain, modulate T. cruzi entry. Measurements of Ca2+-triggered exocytosis of lysosomes in these cell lines revealed an enhancement of beta-hexosaminidase release in cells expressing wild-type Lamp-1 on the plasma membrane; this effect was not observed in cell lines transfected with Lamp-1 cytoplasmic tail mutants. These results also implicate Ca2+-regulated lysosome 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • CHO Cells
  • Calcium / metabolism
  • Cell Membrane / metabolism
  • Chagas Disease / parasitology
  • Cricetinae
  • Exocytosis / physiology*
  • Fluorescent Antibody Technique
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Microtubules / metabolism
  • Transfection
  • Trypanosoma cruzi / pathogenicity*
  • Trypanosoma cruzi / physiology

Substances

  • Antigens, CD
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Glycoproteins
  • Calcium