Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity
The circumsporozoite protein of Plasmodium falciparum contains two conserved motifs (regions I and II) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. To study the function of this...
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Veröffentlicht in: | The Journal of biological chemistry 2002-12, Vol.277 (49), p.47613-47618 |
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creator | Tewari, Rita Spaccapelo, Roberta Bistoni, Francesco Holder, Anthony A Crisanti, Andrea |
description | The circumsporozoite protein of Plasmodium falciparum contains two conserved motifs (regions I and II) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. These data shed new light on the role of the CS protein in sporozoite motility and infectivity. |
doi_str_mv | 10.1074/jbc.M208453200 |
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To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. 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To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. These data shed new light on the role of the CS protein in sporozoite motility and infectivity.</description><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Anopheles - metabolism</subject><subject>Blotting, Southern</subject><subject>Erythrocytes - parasitology</subject><subject>Intestines - parasitology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Fluorescence</subject><subject>Microscopy, Phase-Contrast</subject><subject>Models, Genetic</subject><subject>Molecular Sequence Data</subject><subject>Movement</subject><subject>Plasmodium falciparum - metabolism</subject><subject>Protein Binding</subject><subject>Protozoan Proteins - chemistry</subject><subject>Protozoan Proteins - metabolism</subject><subject>Salivary Glands - parasitology</subject><subject>Sequence Homology, Amino Acid</subject><subject>Sporozoites - metabolism</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDFPwzAQhT2AaCmsjMgTW4p9dmJnRBWFSEUwwBy5jg2ukjjESaUy88NxoUhsnE66d6en706H0AUlc0oEv96s9fwBiOQpA0KO0JQQoEkOqZyg0xA2JAbP6QmaUADOScan6HM5tnpwvsXe4t687lWBVVvhIpbqzQS3Nbjxg7Nhb3mqVWh85cYGW1Vr16k-Su16PTah873_8G4wuOv9YFyLY_6Z7jG1G3bffNdaEzdvY3-GjiMsmPNDnaGX5e3z4j5ZPd4Vi5tV0gGTQyItN4QLngrBwNJMSUmJiRTJcpKCBpIDrzJrmWIyl1rk3EjGKTcpo5Wo2Axd_XDjee-jCUPZuKBNXavW-DGUAgSkQtJ_jVRmQCjwaLw8GMd1Y6qy612j-l35-2D2BT6GfS0</recordid><startdate>20021206</startdate><enddate>20021206</enddate><creator>Tewari, Rita</creator><creator>Spaccapelo, Roberta</creator><creator>Bistoni, Francesco</creator><creator>Holder, Anthony A</creator><creator>Crisanti, Andrea</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20021206</creationdate><title>Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity</title><author>Tewari, Rita ; Spaccapelo, Roberta ; Bistoni, Francesco ; Holder, Anthony A ; Crisanti, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p238t-8f4e047457732f16a8810efec839052c20924d6ff3a3898c794e83414e531d7d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amino Acid Motifs</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Anopheles - metabolism</topic><topic>Blotting, Southern</topic><topic>Erythrocytes - parasitology</topic><topic>Intestines - parasitology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Fluorescence</topic><topic>Microscopy, Phase-Contrast</topic><topic>Models, Genetic</topic><topic>Molecular Sequence Data</topic><topic>Movement</topic><topic>Plasmodium falciparum - metabolism</topic><topic>Protein Binding</topic><topic>Protozoan Proteins - chemistry</topic><topic>Protozoan Proteins - metabolism</topic><topic>Salivary Glands - parasitology</topic><topic>Sequence Homology, Amino Acid</topic><topic>Sporozoites - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tewari, Rita</creatorcontrib><creatorcontrib>Spaccapelo, Roberta</creatorcontrib><creatorcontrib>Bistoni, Francesco</creatorcontrib><creatorcontrib>Holder, Anthony A</creatorcontrib><creatorcontrib>Crisanti, Andrea</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tewari, Rita</au><au>Spaccapelo, Roberta</au><au>Bistoni, Francesco</au><au>Holder, Anthony A</au><au>Crisanti, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-12-06</date><risdate>2002</risdate><volume>277</volume><issue>49</issue><spage>47613</spage><epage>47618</epage><pages>47613-47618</pages><issn>0021-9258</issn><abstract>The circumsporozoite protein of Plasmodium falciparum contains two conserved motifs (regions I and II) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. These data shed new light on the role of the CS protein in sporozoite motility and infectivity.</abstract><cop>United States</cop><pmid>12244064</pmid><doi>10.1074/jbc.M208453200</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Motifs Amino Acid Sequence Animals Animals, Genetically Modified Anopheles - metabolism Blotting, Southern Erythrocytes - parasitology Intestines - parasitology Mice Mice, Inbred BALB C Mice, Transgenic Microscopy, Fluorescence Microscopy, Phase-Contrast Models, Genetic Molecular Sequence Data Movement Plasmodium falciparum - metabolism Protein Binding Protozoan Proteins - chemistry Protozoan Proteins - metabolism Salivary Glands - parasitology Sequence Homology, Amino Acid Sporozoites - metabolism |
title | Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity |
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