The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion
Red blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite sur...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/61121 |
| _version_ | 1818023839101091840 |
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| author | Christine R Collins Fiona Hackett Steven A Howell Ambrosius P Snijders Matthew RG Russell Lucy M Collinson Michael J Blackman |
| author_facet | Christine R Collins Fiona Hackett Steven A Howell Ambrosius P Snijders Matthew RG Russell Lucy M Collinson Michael J Blackman |
| author_sort | Christine R Collins |
| collection | DOAJ |
| description | Red blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite surface proteins are shed by a membrane-bound protease called SUB2. Here we show that genetic depletion of SUB2 abolishes shedding of a range of parasite proteins, identifying previously unrecognized SUB2 substrates. Interaction of SUB2-null merozoites with RBCs leads to either abortive invasion with rapid RBC lysis, or successful entry but developmental arrest. Selective failure to shed the most abundant SUB2 substrate, MSP1, reduces intracellular replication, whilst conditional ablation of the substrate AMA1 produces host RBC lysis. We conclude that SUB2 activity is critical for host RBC membrane sealing following parasite internalisation and for correct functioning of merozoite surface proteins. |
| first_indexed | 2024-12-10T03:50:41Z |
| format | Article |
| id | doaj.art-db80ffd4e5224938a70dac40b370a90c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:50:41Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-db80ffd4e5224938a70dac40b370a90c2022-12-22T02:03:16ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.61121The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasionChristine R Collins0https://orcid.org/0000-0001-5191-7634Fiona Hackett1Steven A Howell2Ambrosius P Snijders3Matthew RG Russell4https://orcid.org/0000-0003-4608-7669Lucy M Collinson5Michael J Blackman6https://orcid.org/0000-0002-7442-3810Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United KingdomMalaria Biochemistry Laboratory, The Francis Crick Institute, London, United KingdomProtein Analysis and Proteomics Platform, The Francis Crick Institute, London, United KingdomProtein Analysis and Proteomics Platform, The Francis Crick Institute, London, United KingdomElectron Microscopy Science Technology Platform, The Francis Crick Institute, London, United KingdomElectron Microscopy Science Technology Platform, The Francis Crick Institute, London, United KingdomMalaria Biochemistry Laboratory, The Francis Crick Institute, London, United Kingdom; Faculty of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United KingdomRed blood cell (RBC) invasion by malaria merozoites involves formation of a parasitophorous vacuole into which the parasite moves. The vacuole membrane seals and pinches off behind the parasite through an unknown mechanism, enclosing the parasite within the RBC. During invasion, several parasite surface proteins are shed by a membrane-bound protease called SUB2. Here we show that genetic depletion of SUB2 abolishes shedding of a range of parasite proteins, identifying previously unrecognized SUB2 substrates. Interaction of SUB2-null merozoites with RBCs leads to either abortive invasion with rapid RBC lysis, or successful entry but developmental arrest. Selective failure to shed the most abundant SUB2 substrate, MSP1, reduces intracellular replication, whilst conditional ablation of the substrate AMA1 produces host RBC lysis. We conclude that SUB2 activity is critical for host RBC membrane sealing following parasite internalisation and for correct functioning of merozoite surface proteins.https://elifesciences.org/articles/61121malariaplasmodiuminvasionsheddaseproteaseerythrocyte |
| spellingShingle | Christine R Collins Fiona Hackett Steven A Howell Ambrosius P Snijders Matthew RG Russell Lucy M Collinson Michael J Blackman The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion eLife malaria plasmodium invasion sheddase protease erythrocyte |
| title | The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion |
| title_full | The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion |
| title_fullStr | The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion |
| title_full_unstemmed | The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion |
| title_short | The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion |
| title_sort | malaria parasite sheddase sub2 governs host red blood cell membrane sealing at invasion |
| topic | malaria plasmodium invasion sheddase protease erythrocyte |
| url | https://elifesciences.org/articles/61121 |
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