Open AccessP. falciparum RH5‐Basigin interaction induces changes in the cytoskeleton of the host RBC
Author(s) -
Aniweh Yaw,
Gao Xiaohong,
Hao Piliang,
Meng Wei,
Lai Soak Kuan,
Gunalan Karthigayan,
Chu Trang T.,
Sinha Ameya,
Lescar Julien,
Chandramohanadas Rajesh,
Li Hoi Yeung,
Sze Siu Kwan,
Preiser Peter R.
Publication year - 2017
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12747
Subject(s) - basigin , biology , cytoskeleton , microbiology and biotechnology , context (archaeology) , reticulocyte , plasmodium falciparum , red blood cell , signal transduction , cell , biochemistry , immunology , malaria , gene , paleontology , messenger rna , matrix metalloproteinase
Summary The successful invasion of Plasmodium is an essential step in their life cycle. The parasite reticulocyte‐binding protein homologues (RHs) and erythrocyte‐binding like proteins are two families involved in the invasion leading to merozoite‐red blood cell (RBC) junction formation. Ca 2+ signaling has been shown to play a critical role in the invasion. RHs have been linked to Ca 2+ signaling, which triggers the erythrocyte‐binding like proteins release ahead of junction formation, consistent with RHs performing an initial sensing function in identifying suitable RBCs. RH5, the only essential RHs, is a highly promising vaccine candidate. RH5‐basigin interaction is essential for merozoite invasion and also important in determining host tropism. Here, we show that RH5 has a distinct function from the other RHs. We show that RH5‐Basigin interaction on its own triggers a Ca 2+ signal in the RBC resulting in changes in RBC cytoskeletal proteins phosphorylation and overall alterations in RBC cytoskeleton architecture. Antibodies targeting RH5 that block the signal prevent invasion before junction formation consistent with the Ca 2+ signal in the RBC leading to rearrangement of the cytoskeleton required for invasion. This work provides the first time a functional context for the essential role of RH5 and will now open up new avenues to target merozoite invasion.