TY - JOUR
T1 - Desialylation of lysosomal membrane glycoproteins by trypanosoma cruzi
T2 - A role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm
AU - Hall, B. Fenton
AU - Webster, Paul
AU - Ma, Anne K.
AU - Joiner, Keith A.
AU - Andrews, Norma W.
PY - 1992/8/1
Y1 - 1992/8/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.176.2.313
DO - 10.1084/jem.176.2.313
M3 - Article
C2 - 1500849
AN - SCOPUS:0026637237
VL - 176
SP - 313
EP - 325
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 2
ER -