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

B. Fenton Hall, Paul Webster, Anne K. Ma, Keith A. Joiner, Norma W. Andrews

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Trypanosoma cmzi 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 rdease 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 deavage 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 protozoanderived 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.

Original languageEnglish (US)
Pages (from-to)313-325
Number of pages13
JournalJournal of Experimental Medicine
Volume176
Issue number2
DOIs
StatePublished - Aug 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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