NDLI: Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans

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Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans

Content Provider	Semantic Scholar
Author	Shakibaei, Mehdi Frevert, Ute
Copyright Year	1996
Abstract	Speed and selectivity of hepatocyte invasion by malaria sporozoites have suggested a receptor-mediated mechanism and the specific interaction of the circumsporozoite (CS) protein with liver-specific heparan sulfate proteoglycans (HSPGs) has been implicated in the targeting to the liver. Here we show that the CS protein interacts not only with cell surface heparan sulfate, but also with the low density lipoprotein receptor-related protein (LRP). Binding of 125I-CS protein to purified LRP occurs with a Kd of 4.9 nM and can be inhibited by the receptor-associated protein (RAP). Blockage of LRP by RAP or anti-LRP antibodies on heparan sulfate-deficient CHO cells results in more than 90% inhibition of binding and endocytosis of recombinant CS protein. Conversely, blockage or enzymatic removal of the cell surface heparan sulfate from LRP-deficient embryonic mouse fibroblasts yields the same degree of inhibition. Heparinase-pretreatment of LRP-deficient fibroblasts or blockage of LRP on heparan sulfate-deficient CHO cells by RAP, lactoferrin, or anti-LRP antibodies reduces Plasmodium berghei invasion by 60-70%. Parasite development in heparinase-pretreated HepG2 cells is inhibited by 65% when RAP is present during sporozoite invasion. These findings suggest that malaria sporozoites utilize the interaction of the CS protein with HSPGs and LRP as the major mechanism for host cell invasion.
Starting Page	1699
Ending Page	1711
Page Count	13
File Format	PDF HTM / HTML
PubMed reference number	8920859
Volume Number	184
Journal	The Journal of experimental medicine
Alternate Webpage(s)	http://jem.rupress.org/content/184/5/1699.full.pdf
Alternate Webpage(s)	http://ftp.ncbi.nlm.nih.gov/pub/pmc/b6/19/je18451699.PMC2192891.pdf
Language	English
Access Restriction	Open
Subject Keyword	Cell Invasion Dual Heparan Sulfate Proteoglycans Heparin Lyase Heparitin Sulfate LTF protein, human Low Density Lipoprotein Receptor Low-Density Lipoproteins Malaria Vaccines Proteoglycan Recombinants Sporozoites circumsporozoite protein entry into host cell
Content Type	Text
Resource Type	Article

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