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Originally published In Press as doi:10.1074/jbc.M104038200 on May 14, 2001

J. Biol. Chem., Vol. 276, Issue 29, 26784-26791, July 20, 2001
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The Binding of the Circumsporozoite Protein to Cell Surface Heparan Sulfate Proteoglycans Is Required for Plasmodium Sporozoite Attachment to Target Cells*

Consuelo Pinzon-OrtizDagger , Jennifer FriedmanDagger , Jeffrey Esko, and Photini SinnisDagger ||

From the Dagger  Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10010 and the  Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093

The major surface protein of malaria sporozoites, the circumsporozoite protein, binds to heparan sulfate proteoglycans on the surface of hepatocytes. It has been proposed that this binding event is responsible for the rapid and specific localization of sporozoites to the liver after their injection into the skin by an infected anopheline mosquito. Previous in vitro studies performed under static conditions have failed to demonstrate a significant role for heparan sulfate proteoglycans during sporozoite invasion of cells. We performed sporozoite attachment and invasion assays under more dynamic conditions and found a dramatic decrease in sporozoite attachment to cells in the presence of heparin. In contrast to its effect on attachment, heparin does not appear to have an effect on sporozoite invasion of cells. When substituted heparins were used as competitive inhibitors of sporozoite attachment, we found that sulfation of the glycosaminoglycan chains at both the N- and O-positions was important for sporozoite adhesion to cells. We conclude that the binding of the circumsporozoite protein to hepatic heparan sulfate proteoglycans is likely to function during sporozoite attachment in the liver and that this adhesion event depends on the sulfated glycosaminoglycan chains of the proteoglycans.


* This work was supported by a grant from the Irma T. Hirschl Charitable Trust (to P. S.) and by National Institutes of Health Grants AI44470-02 (to P. S.) and GM33063 (to J. D. E.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Current address: Dept. of Pediatrics, Boston Children's Hospital, 333 Longwood Ave., 2nd Floor, Health Services Research, Boston, MA 02115.

|| To whom correspondence should be addressed: Dept. of Medical and Molecular Parasitology, New York University School of Medicine, 341 E. 25th St., New York, NY 10010. Tel.: 212-263-6818; Fax: 212-263-8116; E-mail: photini.sinnis@med.nyu.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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