Publication Date:
2014-07-22
Description:
During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that separates the parasite from the host cell cytosol. These proteins have a variety of roles that are essential to virulence or parasite growth. There is keen interest in understanding how proteins are exported and whether common machineries are involved in trafficking the different classes of exported proteins. One potential trafficking machine is a protein complex known as the Plasmodium translocon of exported proteins (PTEX). Although PTEX has been linked to the export of one class of exported proteins, there has been no direct evidence for its role and scope in protein translocation. Here we show, through the generation of two parasite lines defective for essential PTEX components (HSP101 or PTEX150), and analysis of a line lacking the non-essential component TRX2 (ref. 12), greatly reduced trafficking of all classes of exported proteins beyond the double membrane barrier enveloping the parasite. This includes proteins containing the PEXEL motif (RxLxE/Q/D) and PEXEL-negative exported proteins (PNEPs). Moreover, the export of proteins destined for expression on the infected erythrocyte surface, including the major virulence factor PfEMP1 in Plasmodium falciparum, was significantly reduced in PTEX knockdown parasites. PTEX function was also essential for blood-stage growth, because even a modest knockdown of PTEX components had a strong effect on the parasite's capacity to complete the erythrocytic cycle both in vitro and in vivo. Hence, as the only known nexus for protein export in Plasmodium parasites, and an essential enzymic machine, PTEX is a prime drug target.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elsworth, Brendan -- Matthews, Kathryn -- Nie, Catherine Q -- Kalanon, Ming -- Charnaud, Sarah C -- Sanders, Paul R -- Chisholm, Scott A -- Counihan, Natalie A -- Shaw, Philip J -- Pino, Paco -- Chan, Jo-Anne -- Azevedo, Mauro F -- Rogerson, Stephen J -- Beeson, James G -- Crabb, Brendan S -- Gilson, Paul R -- de Koning-Ward, Tania F -- England -- Nature. 2014 Jul 31;511(7511):587-91. doi: 10.1038/nature13555. Epub 2014 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Australia [2] Monash University, Clayton, Victoria, 3800, Australia [3]. ; 1] Deakin University, Waurn Ponds, 3216, Australia [2]. ; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Australia. ; Deakin University, Waurn Ponds, 3216, Australia. ; 1] Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Australia [2] Monash University, Clayton, Victoria, 3800, Australia. ; National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, Thailand. ; The University of Geneva, 1211 Geneva 4, Switzerland. ; The University of Melbourne, Parkville, Victoria, 3010 Australia. ; 1] Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Australia [2] Monash University, Clayton, Victoria, 3800, Australia [3] The University of Melbourne, Parkville, Victoria, 3010 Australia. ; 1] Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Australia [2] Monash University, Clayton, Victoria, 3800, Australia [3] The University of Melbourne, Parkville, Victoria, 3010 Australia [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043043" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Erythrocytes/metabolism/parasitology
;
Heat-Shock Proteins/genetics/*metabolism
;
Humans
;
Life Cycle Stages/physiology
;
Malaria/*parasitology
;
Multiprotein Complexes/metabolism
;
Plasmodium falciparum/*genetics/*metabolism
;
Protein Transport/genetics
;
Protozoan Proteins/genetics/*metabolism
;
Vacuoles/metabolism/parasitology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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