Publication Date:
2014-07-22
Description:
To mediate its survival and virulence, the malaria parasite Plasmodium falciparum exports hundreds of proteins into the host erythrocyte. To enter the host cell, exported proteins must cross the parasitophorous vacuolar membrane (PVM) within which the parasite resides, but the mechanism remains unclear. A putative Plasmodium translocon of exported proteins (PTEX) has been suggested to be involved for at least one class of exported proteins; however, direct functional evidence for this has been elusive. Here we show that export across the PVM requires heat shock protein 101 (HSP101), a ClpB-like AAA+ ATPase component of PTEX. Using a chaperone auto-inhibition strategy, we achieved rapid, reversible ablation of HSP101 function, resulting in a nearly complete block in export with substrates accumulating in the vacuole in both asexual and sexual parasites. Surprisingly, this block extended to all classes of exported proteins, revealing HSP101-dependent translocation across the PVM as a convergent step in the multi-pathway export process. Under export-blocked conditions, association between HSP101 and other components of the PTEX complex was lost, indicating that the integrity of the complex is required for efficient protein export. Our results demonstrate an essential and universal role for HSP101 in protein export and provide strong evidence for PTEX function in protein translocation into the host cell.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130291/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130291/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beck, Josh R -- Muralidharan, Vasant -- Oksman, Anna -- Goldberg, Daniel E -- AI047798/AI/NIAID NIH HHS/ -- AI099156/AI/NIAID NIH HHS/ -- K99 AI099156/AI/NIAID NIH HHS/ -- R01 AI047798/AI/NIAID NIH HHS/ -- T32-AI007172/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 31;511(7511):592-5. doi: 10.1038/nature13574. Epub 2014 Jul 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA [2]. ; 1] Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA [2] Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA [3] [4] Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, USA. ; 1] Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA [2] Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA [3] Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043010" target="_blank"〉PubMed〈/a〉
Keywords:
Erythrocytes/*parasitology
;
Heat-Shock Proteins/*metabolism
;
Host-Parasite Interactions/*physiology
;
Life Cycle Stages/genetics
;
Malaria, Falciparum/*parasitology
;
Plasmodium falciparum/metabolism/pathogenicity/*physiology
;
Protein Transport
;
Protozoan Proteins/*metabolism
;
Vacuoles/parasitology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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