Cell surface glycosaminoglycans are not obligatory for Plasmodium berghei sporozoite invasion in vitro

Ute Frevert, Photini Sinnis, Jeffrey D. Esko, Victor Nussenzweig

Research output: Contribution to journalArticle

Abstract

The malaria circumsporozoite (CS) protein binds to glycosaminoglycan chains from heparan sulfate proteoglycans present on the basolateral surface of hepatocytes and hepatoma cells in vitro. When injected into mice, CS protein is rapidly cleared from the blood circulation by hepatocytes. The binding region for the HSPGs is the evolutionarily conserved region II-plus of the CS protein. Here we have asked whether the presence of glycosaminoglycans on the plasma membrane of target cells is required for sporozoite invasion in vitro. Two types of target cells were used: HepG2 cells, which are permissive for Plasmodium berghei sporozoite development into mature exoerythrocytic forms, and CHO cells, in which the intracellular development of the parasites is arrested early after penetration. The invasion of mutant CHO cells expressing undersulfated glycosaminoglycans or no glycosaminoglycans was only inhibited 41-49% or 24-32%, respectively, in comparison to invasion of CHO-K1 cells. Previous cleavage of HepG2 surface membrane glycosaminoglycans with heparinase or heparitinase had no significant inhibitory effect on subsequent P. berghei sporozoite invasion and EEF development in these cells, although the glycosaminoglycan lyase treatments removed over 80% of CS binding sites from the cell surface. These results suggest that although the presence of glycosaminoglycans on the target cell surface enhances sporozoite invasion, glycosaminoglycans are not required for sporozoite penetration or the development of exoerythrocytic forms in vitro.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalMolecular and Biochemical Parasitology
Volume76
Issue number1-2
DOIs
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

Plasmodium berghei
Sporozoites
Glycosaminoglycans
CHO Cells
Heparan Sulfate Proteoglycans
heparitinsulfate lyase
Hepatocytes
Heparin Lyase
Lyases
In Vitro Techniques
Blood Circulation
Hep G2 Cells
Malaria
Hepatocellular Carcinoma
Parasites
Proteins
Binding Sites
Cell Membrane
Membranes

Keywords

  • circumsporozoite protein
  • heparan sulfate proteoglycan
  • heparan sulfate-deficient CHO mutants
  • Plasmodium berghei
  • sporozoite invasion

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

Cell surface glycosaminoglycans are not obligatory for Plasmodium berghei sporozoite invasion in vitro. / Frevert, Ute; Sinnis, Photini; Esko, Jeffrey D.; Nussenzweig, Victor.

In: Molecular and Biochemical Parasitology, Vol. 76, No. 1-2, 02.1996, p. 257-266.

Research output: Contribution to journalArticle

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