論文 - 詳細
| RRC ID | 67312 |
|---|---|
| 著者 | Real E, Rodrigues L, Cabal GG, Enguita FJ, Mancio-Silva L, Mello-Vieira J, Beatty W, Vera IM, Zuzarte-Luís V, Figueira TN, Mair GR, Mota MM. |
| タイトル | Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy in hepatocytes. |
| ジャーナル | Nat Microbiol |
| Abstract |
The causative agent of malaria, Plasmodium, replicates inside a membrane-bound parasitophorous vacuole (PV), which shields this intracellular parasite from the cytosol of the host cell 1 . One common threat for intracellular pathogens is the homeostatic process of autophagy, through which cells capture unwanted intracellular material for lysosomal degradation 2 . During the liver stage of a malaria infection, Plasmodium parasites are targeted by the autophagy machinery of the host cell, and the PV membrane (PVM) becomes decorated with several autophagy markers, including LC3 (microtubule-associated protein 1 light chain 3) 3,4 . Here we show that Plasmodium berghei parasites infecting hepatic cells rely on the PVM transmembrane protein UIS3 to avoid elimination by host-cell-mediated autophagy. We found that UIS3 binds host LC3 through a non-canonical interaction with a specialized surface on LC3 where host proteins with essential functions during autophagy also bind. UIS3 acts as a bona fide autophagy inhibitor by competing with host LC3-interacting proteins for LC3 binding. Our work identifies UIS3, one of the most promising candidates for a genetically attenuated vaccine against malaria 5 , as a unique and potent mediator of autophagy evasion in Plasmodium. We propose that the protein-protein interaction between UIS3 and host LC3 represents a target for antimalarial drug development. |
| 巻・号 | 3(1) |
| ページ | 17-25 |
| 公開日 | 2018-1-1 |
| DOI | 10.1038/s41564-017-0054-x |
| PII | 10.1038/s41564-017-0054-x |
| PMID | 29109477 |
| PMC | PMC5739284 |
| MeSH | Animals Autophagosomes / metabolism Autophagy / physiology* Cell Line HEK293 Cells Hep G2 Cells Hepatocytes / parasitology Hepatocytes / pathology* Hepatocytes / ultrastructure Host-Pathogen Interactions Humans Malaria / parasitology* Malaria / pathology* Malaria / physiopathology Male Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Inbred C57BL Microtubule-Associated Proteins / metabolism* Models, Molecular Plasmodium berghei / genetics* Plasmodium berghei / metabolism Plasmodium berghei / pathogenicity Protein Binding Protozoan Proteins / genetics Protozoan Proteins / metabolism Vacuoles / metabolism |
| IF | 15.54 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 46 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) |