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PMID: 8478608 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Malaria circumsporozoite protein binds to heparan sulfate proteoglycans associated with the surface membrane of hepatocytes.

The Journal of experimental medicine ·Vol. 177 ·No. 5 ·1993-05-01 ·Pages 1287-98

Frevert U, Sinnis P, Cerami C, Shreffler W, Takacs B, Nussenzweig V

Abstract

During feeding by infected mosquitoes, malaria sporozoites are injected into the host's bloodstream and enter hepatocytes within minutes. The remarkable target cell specificity of this parasite may be explained by the presence of receptors for the region II-plus of the circumsporozoite protein (CS) on the basolateral domain of the plasma membrane of hepatocytes. We have now identified these receptors as heparan sulfate proteoglycans (HSPG). The binding of CS to the receptors is abolished by heparitinase treatment, indicating that the recognition of region II-plus is via the glycosaminoglycan chains. We have purified and partially characterized the CS-binding HSPGs from HepG2 cells. They have a molecular weight of 400,000-700,000, are tightly associated with the plasma membrane, and are released from the cell surface by very mild trypsinization, a property which the CS receptors share with the syndecan family of proteoglycans.

MeSH Terms
Amino Acid Sequence Animals Basement Membrane/metabolism Binding Sites Carbohydrate Sequence Cell Membrane/metabolism Epithelium/metabolism Heparan Sulfate Proteoglycans Heparitin Sulfate/isolation & purification,metabolism Kidney Tubules, Proximal/metabolism,ultrastructure Liver/cytology,metabolism,ultrastructure Mast Cells/metabolism,ultrastructure Microscopy, Immunoelectron Molecular Sequence Data Plasmodium falciparum/metabolism Polysaccharide-Lyases/metabolism Proteoglycans/isolation & purification,metabolism Protozoan Proteins/metabolism Rats
Chemicals
Heparan Sulfate Proteoglycans Proteoglycans Protozoan Proteins circumsporozoite protein, Protozoan Heparitin Sulfate Polysaccharide-Lyases heparitinsulfate lyase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Frevert U
Michael Heidelberger Division of Immunology, Department of Pathology, Kaplan Cancer Center, NYU Medical Center, New York 10016.
Sinnis P
Cerami C
Shreffler W
Takacs B
Nussenzweig V
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1993-05-01
Pages
1287-98
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2190997
Subset
IM
Grants
NIAID NIH HHS · K11 AI001175-05 · United States
NCI NIH HHS · 5T32CA9161-16 · United States
NIGMS NIH HHS · 5T32GM07308 · United States
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