Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum

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Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum

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Title: Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum
Author: Brancucci, Nicolas M.B.; Gerdt, Joseph P.; Wang, ChengQi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R.; Zhang, Min; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D.; Laffitte, Marie-Claude; Clark, Martha A.; Grüring, Christof; Ravel, Deepali; Blancke Soares, Alexandra; Demas, Allison; Bopp, Selina; Rubio-Ruiz, Belén; Conejo-Garcia, Ana; Wirth, Dyann F.; Gendaszewska-Darmach, Edyta; Duraisingh, Manoj T.; Adams, John H.; Voss, Till S.; Waters, Andrew P.; Jiang, Rays H.Y.; Clardy, Jon; Marti, Matthias

Note: Order does not necessarily reflect citation order of authors.

Citation: Brancucci, N. M., J. P. Gerdt, C. Wang, M. De Niz, N. Philip, S. R. Adapa, M. Zhang, et al. 2017. “Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.” Cell 171 (7): 1532-1544.e15. doi:10.1016/j.cell.2017.10.020. http://dx.doi.org/10.1016/j.cell.2017.10.020.
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Abstract: Summary Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission.
Published Version: doi:10.1016/j.cell.2017.10.020
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733390/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651946
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