Journal
JOURNAL OF CELL SCIENCE
Volume 134, Issue 5, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.233775
Keywords
Optical tweezers; Gliding motility; Malaria; Plasmodium; Sporozoite; Profilin; Cell motility
Categories
Funding
- Chica and Heinz Schaller Foundation (Chica and Heinz Schaller-Stiftung)
- Human Frontier Science Program [RGY0071/2011]
- European Research Council [StG 281719]
- Heidelberg University (Universitat Heidelberg)
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [240245660 - SFB 1129]
- Academy of Finland [257537, 265112, 292718]
- Jane and Aatos Erkko Foundation (Jane ja Aatos Erkon Saatio)
- Sigrid Juselius foundation (Sigrid Juseliuksen Saatio)
- Emil Aaltonen Foundation (Emil Aaltosen Saatio)
- Burroughs Wellcome Fund
- Klaus Tschira Foundation (Klaus Tschira Stiftung)
- Academy of Finland (AKA) [265112, 257537, 265112, 292718, 292718, 257537] Funding Source: Academy of Finland (AKA)
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Research has shown that the generation of force during Plasmodium sporozoite migration inversely correlates with increased retrograde flow, indicating that slowing down flow to generate force is a key principle governing the parasite's gliding motility.
During transmission of malaria-causing parasites from mosquito to mammal, Plasmodium sporozoites migrate at high speed within the skin to access the bloodstream and infect the liver. This unusual gliding motility is based on retrograde flow of membrane proteins and highly dynamic actin filaments that provide short tracks for a myosin motor. Using laser tweezers and parasite mutants, we previously suggested that actin filaments form macromolecular complexes with plasma membrane-spanning adhesins to generate force during migration. Mutations in the actin-binding region of profilin, a near ubiquitous actin-binding protein, revealed that loss of actin binding also correlates with loss of force production and motility. Here, we show that different mutations in profilin, that do not affect actin binding in vitro, still generate lower force during Plasmodium sporozoite migration. Lower force generation inversely correlates with increased retrograde flow suggesting that, like in mammalian cells, the slow down of flow to generate force is the key underlying principle governing Plasmodium gliding motility.
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