Desialylation of lysosomal membrane glycoproteins by Trypanosoma cruzi : a role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm

• Published in: The Journal of experimental medicine Vol. 176; no. 2; pp. 313 - 325
• Main Authors: HALL, B. F, WEBSTER, P, MA, A. K, JOINER, K. A, ANDREWS, N. W
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01-08-1992; The Rockefeller University Press
• Subjects: activity; Animals; Antigens, CD; Biological and medical sciences; Cell Line; CHO Cells; Cricetinae; cytoplasm; Cytoplasm - parasitology; entry; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; hosts; Hydrogen-Ion Concentration; Invertebrates; Life cycle. Host-agent relationship. Pathogenesis; Lysosomal Membrane Proteins; lysosomes; Lysosomes - metabolism; Lysosomes - ultrastructure; membrane glycoproteins; Membrane Glycoproteins - metabolism; Microscopy, Electron; N-Acetylneuraminic Acid; Neuraminidase - metabolism; Protozoa; Sialic Acids - metabolism; sialidase; Substrate Specificity; Trypanosoma cruzi; Trypanosoma cruzi - enzymology; Trypanosoma cruzi - pathogenicity; Protozoa; Host parasite relation; Enzyme; Lysosome; Glycoproteins; Vacuole; Cell surface; Trypanosoma cruzi; Vertebrata; Mammalia; Enzymatic activity; Neuraminidase; Rhizoflagellata
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.176.2.313

Trypanosoma cruzi enters host cells via formation of an acidic vacuole which is subsequently disrupted, allowing the parasite access to the cytoplasm. We show that in an acid environment, release of the parasite surface neuraminidase is enhanced, and this release is likely mediated by a phosphatidylinositol-specific phospholipase C (PIPLC), since antibodies to a carbohydrate epitope (CRD) revealed in glycosylphosphatidylinositol (GPI)-anchored proteins after PIPLC cleavage remove the great majority of the soluble neuraminidase activity from culture supernatants. The neuraminidase is active at acidic pH, and is capable of desialylating known vacuolar constituents, i.e., lysosomal membrane glycoproteins. Parasite escape into the cytoplasm is significantly facilitated in terminal sialylation-defective mutant Lec 2 cells, and enzymatically desialylated membranes are more susceptible to lysis by a parasite hemolysin previously implicated in vacuole membrane rupture. These findings provide evidence that terminal sialylation on carbohydrate moieties contributes to maintaining lysosomal membrane integrity, and indicate a role for a protozoan-derived neuraminidase in facilitating parasite entry into host cells. These observations raise the possibility that other microbial neuraminidases may serve a similar function in acidic intracellular compartments.