Single-molecule imaging and quantification of the immune-variant adhesin VAR2CSA on knobs of Plasmodium falciparum-infected erythrocytes
- PfEMP1 (erythrocyte membrane protein 1) adhesins play a pivotal role in the pathophysiology of falciparum malaria, by mediating sequestration of Plasmodium falciparum-infected erythrocytes in the microvasculature. PfEMP1 variants are expressed by var genes and are presented on membrane elevations, termed knobs. However, the organization of PfEMP1 on knobs is largely unclear. Here, we use super-resolution microscopy and genetically altered parasites expressing a modified var2csa gene in which the coding sequence of the photoactivatable mEOS2 was inserted to determine the number and distribution of PfEMP1 on single knobs. The data were verified by quantitative fluorescence-activated cell sorting analysis and immuno-electron microscopy together with stereology methods. We show that knobs contain 3.3 ± 1.7 and 4.3 ± 2.5 PfEMP1 molecules, predominantly placed on the knob tip, in parasitized erythrocytes containing wild type and sickle haemoglobin, respectively. The ramifications of our findings for cytoadhesion and immune evasion are discussed.
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| Author: | Cecilia P. Sanchez, Christos KarathanasisORCiDGND, Rodrigo Sanchez, Marek Cyrklaff, Julia Jäger, Bernd Buchholz, Ulrich S. Schwarz, Mike HeilemannORCiDGND, Michael Lanzer |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-503239 |
| DOI: | https://doi.org/10.1038/s42003-019-0429-z |
| ISSN: | 2399-3642 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31098405 |
| Parent Title (English): | Communications biology |
| Publisher: | Springer Nature |
| Place of publication: | London |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2019 |
| Date of first Publication: | 2019/05/08 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2019/05/23 |
| Tag: | Malaria; Parasite immune evasion; Parasitic infection |
| Volume: | 2 |
| Issue: | Art. 172 |
| Page Number: | 9 |
| First Page: | 1 |
| Last Page: | 9 |
| Note: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 453767540 |
| Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
