Intramembrane Cleavage of AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mode
Apicomplexan parasites invade host cells and immediately initiate cell division. The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understoo...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 2011-01, Vol.331 (6016), p.473-477 |
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creator | Santos, Joana M Ferguson, David J.P Blackman, Michael J Soldati-Favre, Dominique |
description | Apicomplexan parasites invade host cells and immediately initiate cell division. The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode. |
doi_str_mv | 10.1126/science.1199284 |
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The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1199284</identifier><identifier>PMID: 21205639</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Antigens ; Antigens, Protozoan - chemistry ; Antigens, Protozoan - genetics ; Antigens, Protozoan - metabolism ; Biological and medical sciences ; Blocking ; Cell Cycle ; Cell Division ; Cell Membrane - metabolism ; Cell membranes ; Cells, Cultured ; Cleavage ; Daughter cells ; Fibroblasts - parasitology ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Humans ; Life cycle. Host-agent relationship. Pathogenesis ; Malaria ; Membrane Proteins - chemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membranes ; Movement ; Mutant Proteins - metabolism ; Organelles ; Parasite hosts ; Parasites ; Parasitic protozoa ; Parasitism ; Phenotypes ; Plasmodium ; Plasmodium falciparum ; Proteins ; Protozoa ; Protozoan Proteins - chemistry ; Protozoan Proteins - genetics ; Protozoan Proteins - metabolism ; Replication ; Serine Proteases - genetics ; Serine Proteases - metabolism ; Signal Transduction ; Switches ; Toxoplasma ; Toxoplasma - cytology ; Toxoplasma - growth & development ; Toxoplasma - physiology ; Vacuoles ; Vector-borne diseases</subject><ispartof>Science (American Association for the Advancement of Science), 2011-01, Vol.331 (6016), p.473-477</ispartof><rights>Copyright © 2011 American Association for the Advancement of Science</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-5691276a11f2c77dd572034f910f65c591711a4c45e096c94ab9a6015160efe33</citedby><cites>FETCH-LOGICAL-c505t-5691276a11f2c77dd572034f910f65c591711a4c45e096c94ab9a6015160efe33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25790185$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25790185$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27903,27904,57995,58228</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23810951$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21205639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Santos, Joana M</creatorcontrib><creatorcontrib>Ferguson, David J.P</creatorcontrib><creatorcontrib>Blackman, Michael J</creatorcontrib><creatorcontrib>Soldati-Favre, Dominique</creatorcontrib><title>Intramembrane Cleavage of AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mode</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Apicomplexan parasites invade host cells and immediately initiate cell division. The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode.</description><subject>Antigens</subject><subject>Antigens, Protozoan - chemistry</subject><subject>Antigens, Protozoan - genetics</subject><subject>Antigens, Protozoan - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blocking</subject><subject>Cell Cycle</subject><subject>Cell Division</subject><subject>Cell Membrane - metabolism</subject><subject>Cell membranes</subject><subject>Cells, Cultured</subject><subject>Cleavage</subject><subject>Daughter cells</subject><subject>Fibroblasts - parasitology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Malaria</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membranes</subject><subject>Movement</subject><subject>Mutant Proteins - metabolism</subject><subject>Organelles</subject><subject>Parasite hosts</subject><subject>Parasites</subject><subject>Parasitic protozoa</subject><subject>Parasitism</subject><subject>Phenotypes</subject><subject>Plasmodium</subject><subject>Plasmodium falciparum</subject><subject>Proteins</subject><subject>Protozoa</subject><subject>Protozoan Proteins - chemistry</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - metabolism</subject><subject>Replication</subject><subject>Serine Proteases - genetics</subject><subject>Serine Proteases - metabolism</subject><subject>Signal Transduction</subject><subject>Switches</subject><subject>Toxoplasma</subject><subject>Toxoplasma - cytology</subject><subject>Toxoplasma - growth & development</subject><subject>Toxoplasma - physiology</subject><subject>Vacuoles</subject><subject>Vector-borne diseases</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1vEzEQxS0EoqFw5gRYSBVcls74a9fHKKIQqRUSTc8rx7HDRrvr1N4E-O_xKguVOMDJGr_fPOvpmZCXCB8QmbpMtnG9dXnQmlXiEZkhaFloBvwxmQFwVVRQyjPyLKUdQNY0f0rOGDKQiusZsct-iKZz3Tqa3tFF68zRbB0Nns5v5khXsdluXUx0FX6EfWtSZ-gQ6O33ZrDfqI-ho6any_5oUnN0o2ToV7dvG2uG8eImbNxz8sSbNrkX03lO7q4-rhafi-svn5aL-XVhJcihkEojK5VB9MyW5WYjyxxDeI3glbRSY4lohBXSgVZWC7PWRgFKVOC84_ycvDv57mO4P7g01F2TrGvbnCwcUq2hRCkVK_9LVqLiDEHITL7_J4lKMIZaVKPp27_QXTjEPifOfqViHARm6PIE2RhSis7X-9h0Jv6sEeqx0nqqtJ4qzRuvJ9vDunObP_zvDjNwMQEmWdP6XKRt0gPHq_FPjE-_OnG7NIT4oMtSA1Zj1Dcn3ZtQm23MHne3DJADai6l1vwXMn26Gg</recordid><startdate>20110128</startdate><enddate>20110128</enddate><creator>Santos, Joana M</creator><creator>Ferguson, David J.P</creator><creator>Blackman, Michael J</creator><creator>Soldati-Favre, Dominique</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>20110128</creationdate><title>Intramembrane Cleavage of AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mode</title><author>Santos, Joana M ; Ferguson, David J.P ; Blackman, Michael J ; Soldati-Favre, Dominique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-5691276a11f2c77dd572034f910f65c591711a4c45e096c94ab9a6015160efe33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antigens</topic><topic>Antigens, Protozoan - chemistry</topic><topic>Antigens, Protozoan - genetics</topic><topic>Antigens, Protozoan - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blocking</topic><topic>Cell Cycle</topic><topic>Cell Division</topic><topic>Cell Membrane - metabolism</topic><topic>Cell membranes</topic><topic>Cells, Cultured</topic><topic>Cleavage</topic><topic>Daughter cells</topic><topic>Fibroblasts - parasitology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Malaria</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Membranes</topic><topic>Movement</topic><topic>Mutant Proteins - metabolism</topic><topic>Organelles</topic><topic>Parasite hosts</topic><topic>Parasites</topic><topic>Parasitic protozoa</topic><topic>Parasitism</topic><topic>Phenotypes</topic><topic>Plasmodium</topic><topic>Plasmodium falciparum</topic><topic>Proteins</topic><topic>Protozoa</topic><topic>Protozoan Proteins - chemistry</topic><topic>Protozoan Proteins - genetics</topic><topic>Protozoan Proteins - metabolism</topic><topic>Replication</topic><topic>Serine Proteases - genetics</topic><topic>Serine Proteases - metabolism</topic><topic>Signal Transduction</topic><topic>Switches</topic><topic>Toxoplasma</topic><topic>Toxoplasma - cytology</topic><topic>Toxoplasma - growth & development</topic><topic>Toxoplasma - physiology</topic><topic>Vacuoles</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Santos, Joana M</creatorcontrib><creatorcontrib>Ferguson, David J.P</creatorcontrib><creatorcontrib>Blackman, Michael J</creatorcontrib><creatorcontrib>Soldati-Favre, Dominique</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>21205639</pmid><doi>10.1126/science.1199284</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antigens Antigens, Protozoan - chemistry Antigens, Protozoan - genetics Antigens, Protozoan - metabolism Biological and medical sciences Blocking Cell Cycle Cell Division Cell Membrane - metabolism Cell membranes Cells, Cultured Cleavage Daughter cells Fibroblasts - parasitology Fundamental and applied biological sciences. Psychology Gene expression Humans Life cycle. Host-agent relationship. Pathogenesis Malaria Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Membranes Movement Mutant Proteins - metabolism Organelles Parasite hosts Parasites Parasitic protozoa Parasitism Phenotypes Plasmodium Plasmodium falciparum Proteins Protozoa Protozoan Proteins - chemistry Protozoan Proteins - genetics Protozoan Proteins - metabolism Replication Serine Proteases - genetics Serine Proteases - metabolism Signal Transduction Switches Toxoplasma Toxoplasma - cytology Toxoplasma - growth & development Toxoplasma - physiology Vacuoles Vector-borne diseases |
title | Intramembrane Cleavage of AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mode |
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