{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:33:41Z","timestamp":1791272021494,"version":"4.1.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Malaria pathology is linked to remodeling of red blood cells by eukaryotic\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            parasites. Central to host cell refurbishment is the trafficking of parasite-encoded virulence factors through the\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            translocon of exported proteins (PTEX). Much of our understanding of its function is based on experimental work with cultured\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            , yet direct consequences of PTEX impairment during an infection remain poorly defined. Using the murine malaria model parasite\n            <jats:named-content content-type=\"genus-species\">Plasmodium berghei<\/jats:named-content>\n            , it is shown here that efficient sequestration to the pulmonary, adipose, and brain tissue vasculature is dependent on the PTEX components thioredoxin 2 (TRX2) and PTEX88. While\n            <jats:italic>TRX2<\/jats:italic>\n            -deficient parasites remain virulent,\n            <jats:italic>PTEX88<\/jats:italic>\n            -deficient parasites no longer sequester in the brain, correlating with abolishment of cerebral complications in infected mice. However, an apparent trade-off for virulence attenuation was spleen enlargement, which correlates with a strongly reduced schizont-to-ring-stage transition. Strikingly, general protein export is unaffected in\n            <jats:italic>PTEX88<\/jats:italic>\n            -deficient mutants that mature normally\n            <jats:italic>in vitro<\/jats:italic>\n            . Thus, PTEX88 is pivotal for tissue sequestration\n            <jats:italic>in vivo<\/jats:italic>\n            , parasite virulence, and preventing exacerbation of spleen pathology, but these functions do not correlate with general protein export to the host erythrocyte. The presented data suggest that the protein export machinery of\n            <jats:named-content content-type=\"genus-species\">Plasmodium<\/jats:named-content>\n            parasites and their underlying mechanistic features are considerably more complex than previously anticipated and indicate challenges for targeted intervention strategies.\n          <\/jats:p>","DOI":"10.1128\/ec.00276-14","type":"journal-article","created":{"date-parts":[[2015,3,28]],"date-time":"2015-03-28T18:07:24Z","timestamp":1427566044000},"page":"528-534","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["<i>In Vivo<\/i>\n            Function of PTEX88 in Malaria Parasite Sequestration and Virulence"],"prefix":"10.1128","volume":"14","author":[{"given":"Joachim M.","family":"Matz","sequence":"first","affiliation":[{"name":"Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany"},{"name":"Institute of Biology, Humboldt University, Berlin, Germany"},{"name":"Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Ingmundson","sequence":"additional","affiliation":[{"name":"Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Costa Nunes","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Charit\u00e9\u2013Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Stenzel","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Charit\u00e9\u2013Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Matuschewski","sequence":"additional","affiliation":[{"name":"Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany"},{"name":"Institute of Biology, Humboldt University, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8547-7523","authenticated-orcid":false,"given":"Taco W. A.","family":"Kooij","sequence":"additional","affiliation":[{"name":"Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany"},{"name":"Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands"},{"name":"Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.2.010506.091913"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2012.07.011"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092412-155730"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.04.051"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01741.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir812"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1102737"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1102452"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.09.010"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M112.021238"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08104"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12334"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2013.09.003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13574"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13555"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1179\/2047773215Y.0000000006"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2005.09.007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2006.00706.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030085"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000086"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08004.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503386102"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001032"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00104"},{"key":"e_1_3_3_26_2","first-page":"103","article-title":"Experimental models of cerebral malaria","volume":"297","author":"Engwerda C","year":"2005","unstructured":"Engwerda C, Belnoue E, Gr\u00fcner AC, R\u00e9nia L. 2005. Experimental models of cerebral malaria. 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