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 Citations (Scopus)

Abstract

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 Lee 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.

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

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Lysosome-Associated Membrane Glycoproteins
Trypanosoma cruzi
Neuraminidase
Cytoplasm
Parasites
Phosphoinositide Phospholipase C
Vacuoles
Membranes
Carbohydrates
Glycosylphosphatidylinositols
Hemolysin Proteins
Epitopes
Rupture
Acids
Antibodies
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Desialylation of lysosomal membrane glycoproteins by Trypanosoma cruzi : A role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm. / Hall, B. Fenton; Webster, Paul; Ma, Anne K.; Joiner, Keith A; Andrews, Norma W.

In: Journal of Experimental Medicine, Vol. 176, No. 2, 01.08.1992, p. 313-325.

Research output: Contribution to journalArticle

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