Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family
ABSTRACT During its intraerythrocytic development, the malaria parasite Plasmodium falciparum exposes variant surface antigens (VSAs) on infected erythrocytes to establish and maintain an infection. One family of small VSAs is the polymorphic STEVOR proteins, which are marked for export to the host...
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American Society for Microbiology
2019
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oai:doaj.org-article:517410248da74ba7892762b5ae7fb3442021-11-15T16:22:11ZDissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family10.1128/mBio.01500-192150-7511https://doaj.org/article/517410248da74ba7892762b5ae7fb3442019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01500-19https://doaj.org/toc/2150-7511ABSTRACT During its intraerythrocytic development, the malaria parasite Plasmodium falciparum exposes variant surface antigens (VSAs) on infected erythrocytes to establish and maintain an infection. One family of small VSAs is the polymorphic STEVOR proteins, which are marked for export to the host cell surface through their PEXEL signal peptide. Interestingly, some STEVORs have also been reported to localize to the parasite plasma membrane and apical organelles, pointing toward a putative function in host cell egress or invasion. Using deep RNA sequencing analysis, we characterized P. falciparum stevor gene expression across the intraerythrocytic development cycle, including free merozoites, in detail and used the resulting stevor expression profiles for hierarchical clustering. We found that most stevor genes show biphasic expression oscillation, with maximum expression during trophozoite stages and a second peak in late schizonts. We selected four STEVOR variants, confirmed the expected export of these proteins to the host cell membrane, and tracked them to a secondary location, either to the parasite plasma membrane or the secretory organelles of merozoites in late schizont stages. We investigated the function of a particular STEVOR that showed rhoptry localization and demonstrated its role at the parasite-host interface during host cell invasion by specific antisera and targeted gene disruption. Experimentally determined membrane topology of this STEVOR revealed a single transmembrane domain exposing the semiconserved as well as variable protein regions to the cell surface. IMPORTANCE Malaria claims about half a million lives each year. Plasmodium falciparum, the causative agent of the most severe form of the disease, uses proteins that are translocated to the surface of infected erythrocytes for immune evasion. To circumvent the detection of these gene products by the immune system, the parasite evolved a complex strategy that includes gene duplications and elaborate sequence polymorphism. STEVORs are one family of these variant surface antigens and are encoded by about 40 genes. Using deep RNA sequencing of blood-stage parasites, including free merozoites, we first established stevor expression of the cultured isolate and compared it with published transcriptomes. We reveal a biphasic expression of most stevor genes and confirm this for individual STEVORs at the protein level. The membrane topology of a rhoptry-associated variant was experimentally elucidated and linked to host cell invasion, underlining the importance of this multifunctional protein family for parasite proliferation.J. Stephan WichersJudith A. M. ScholzJan StraussSusanne WittAndrés LillLaura-Isabell EhnoldNiklas NeupertBenjamin LiffnerRenke LühkenMichaela PetterStephan LorenzenDanny W. WilsonChristian LöwCatherine LavazecIris BruchhausEgbert TannichTim W. GilbergerAnna BachmannAmerican Society for Microbiologyarticlehost cell invasionmalariavariant surface antigensMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019) |
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| collection |
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EN |
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host cell invasion malaria variant surface antigens Microbiology QR1-502 |
| spellingShingle |
host cell invasion malaria variant surface antigens Microbiology QR1-502 J. Stephan Wichers Judith A. M. Scholz Jan Strauss Susanne Witt Andrés Lill Laura-Isabell Ehnold Niklas Neupert Benjamin Liffner Renke Lühken Michaela Petter Stephan Lorenzen Danny W. Wilson Christian Löw Catherine Lavazec Iris Bruchhaus Egbert Tannich Tim W. Gilberger Anna Bachmann Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family |
| description |
ABSTRACT During its intraerythrocytic development, the malaria parasite Plasmodium falciparum exposes variant surface antigens (VSAs) on infected erythrocytes to establish and maintain an infection. One family of small VSAs is the polymorphic STEVOR proteins, which are marked for export to the host cell surface through their PEXEL signal peptide. Interestingly, some STEVORs have also been reported to localize to the parasite plasma membrane and apical organelles, pointing toward a putative function in host cell egress or invasion. Using deep RNA sequencing analysis, we characterized P. falciparum stevor gene expression across the intraerythrocytic development cycle, including free merozoites, in detail and used the resulting stevor expression profiles for hierarchical clustering. We found that most stevor genes show biphasic expression oscillation, with maximum expression during trophozoite stages and a second peak in late schizonts. We selected four STEVOR variants, confirmed the expected export of these proteins to the host cell membrane, and tracked them to a secondary location, either to the parasite plasma membrane or the secretory organelles of merozoites in late schizont stages. We investigated the function of a particular STEVOR that showed rhoptry localization and demonstrated its role at the parasite-host interface during host cell invasion by specific antisera and targeted gene disruption. Experimentally determined membrane topology of this STEVOR revealed a single transmembrane domain exposing the semiconserved as well as variable protein regions to the cell surface. IMPORTANCE Malaria claims about half a million lives each year. Plasmodium falciparum, the causative agent of the most severe form of the disease, uses proteins that are translocated to the surface of infected erythrocytes for immune evasion. To circumvent the detection of these gene products by the immune system, the parasite evolved a complex strategy that includes gene duplications and elaborate sequence polymorphism. STEVORs are one family of these variant surface antigens and are encoded by about 40 genes. Using deep RNA sequencing of blood-stage parasites, including free merozoites, we first established stevor expression of the cultured isolate and compared it with published transcriptomes. We reveal a biphasic expression of most stevor genes and confirm this for individual STEVORs at the protein level. The membrane topology of a rhoptry-associated variant was experimentally elucidated and linked to host cell invasion, underlining the importance of this multifunctional protein family for parasite proliferation. |
| format |
article |
| author |
J. Stephan Wichers Judith A. M. Scholz Jan Strauss Susanne Witt Andrés Lill Laura-Isabell Ehnold Niklas Neupert Benjamin Liffner Renke Lühken Michaela Petter Stephan Lorenzen Danny W. Wilson Christian Löw Catherine Lavazec Iris Bruchhaus Egbert Tannich Tim W. Gilberger Anna Bachmann |
| author_facet |
J. Stephan Wichers Judith A. M. Scholz Jan Strauss Susanne Witt Andrés Lill Laura-Isabell Ehnold Niklas Neupert Benjamin Liffner Renke Lühken Michaela Petter Stephan Lorenzen Danny W. Wilson Christian Löw Catherine Lavazec Iris Bruchhaus Egbert Tannich Tim W. Gilberger Anna Bachmann |
| author_sort |
J. Stephan Wichers |
| title |
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family |
| title_short |
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family |
| title_full |
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family |
| title_fullStr |
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family |
| title_full_unstemmed |
Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the <named-content content-type="genus-species">Plasmodium falciparum</named-content> STEVOR Protein Family |
| title_sort |
dissecting the gene expression, localization, membrane topology, and function of the <named-content content-type="genus-species">plasmodium falciparum</named-content> stevor protein family |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/517410248da74ba7892762b5ae7fb344 |
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