Malaria transmission relies on concavin-mediated maintenance of Plasmodium sporozoite cell shape

Kehrer, J.; Formaglio, P.; Muthinja, J. M.; Weber, S.; Baltissen, D.; Lance, C.; Ripp, J.; Grech, J.; Meissner, M.; Funaya, C.; Amino, R.; Frischknecht, F.

doi:10.1101/2021.11.06.467543

bioRxiv · 10.1101/2021.11.06.467543

Malaria transmission relies on concavin-mediated maintenance of Plasmodium sporozoite cell shape

Kehrer, J.·Formaglio, P.·Muthinja, J. M.·Weber, S.·Baltissen, D.·Lance, C.·Ripp, J.·Grech, J.·Meissner, M.·Funaya, C.·Amino, R.·Frischknecht, F.

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Abstract

During transmission of malaria-causing parasites from mosquitoes to mammals, Plasmodium sporozoites migrate rapidly in the skin to search for a blood vessel. The high migratory speed and narrow passages taken by the parasites suggest considerable strain on the sporozoites to maintain their shape. Here we report on a newly identified protein, concavin, that is important for maintenance of the sporozoite shape inside salivary glands of mosquitoes and during migration in the skin. Concavin-GFP localized at the cytoplasmic periphery of sporozoites and concavin(-) sporozoites progressively rounded up upon entry of salivary glands. These rounded concavin(-) sporozoites failed to pass through the narrow salivary ducts and were hence rarely ejected by mosquitoes. However, normally shaped concavin(-) sporozoites could be transmitted and migrated in the skin or skin like environments. Strikingly, motile concavin(-) sporozoites could disintegrate while migrating through narrow strictures in the skin leading to parasite arrest or death and decreased transmission efficiency. We suggest that concavin contributes to cell shape maintenance by riveting the plasma membrane to the subtending inner membrane complex. SIGNIFICANCEMalaria parasites are transmitted by Anopheles mosquitoes and rely on rapid migration for establishing an infection. We identified and characterized a protein, named concavin, essential for maintaining the shape of the sporozoite. Concavin is a membrane associated protein facing the cytoplasm suggesting that it contributes to riveting the plasma membrane to the subtending inner membrane complex. Sporozoites lacking concavin can round up in the salivary glands, are less well transmitted to mice and disintegrate while migrating in the skin. Hence, concavin is essential for parasite transmission and infectivity. Highlights- A membrane associated protein is essential for Plasmodium shape maintenance -Migrating parasites disintegrate in the absence of concavin -First protein essential for cellular integrity of Plasmodium sporozoites -Thickened and deformed Plasmodium sporozoites fail to be transmitted by mosquitoes

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Kehrer, J., Formaglio, P., Muthinja, J. M., Weber, S., Baltissen, D., Lance, C., Ripp, J., Grech, J., Meissner, M., Funaya, C., Amino, R., Frischknecht, F.. 2021-11-06. Malaria transmission relies on concavin-mediated maintenance of Plasmodium sporozoite cell shape. https://doi.org/10.1101/2021.11.06.467543

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