A female gametocyte-specific ABC transporter plays a role in lipid metabolism in the malaria parasite

Phuong N. Tran; Simon H.J. Brown; Todd W. Mitchell; Kai Matuschewski; Paul J. McMillan; Kiaran Kirk; Matthew W.A. Dixon; Alexander G. Maier

doi:10.1038/ncomms5773

A female gametocyte-specific ABC transporter plays a role in lipid metabolism in the malaria parasite

Phuong N. Tran, Simon H.J. Brown, Todd W. Mitchell, Kai Matuschewski, Paul J. McMillan, Kiaran Kirk, Matthew W.A. Dixon, Alexander G. Maier^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

Abstract

ATP-binding cassette (ABC) transporters serve a variety of physiological functions as well as play key roles in drug resistance. The genome of the human malaria parasite, Plasmodium falciparum, encodes multiple members of this family, one of which, gABCG2, is transcribed predominantly in the gametocyte stage. Here we use gene deletion and tagging to investigate the expression, localization and function of gABCG2. The protein is found in a single dot-like lipid-rich structure within female, but not male, gametocytes. gABCG2-knockout cell lines produce more gametocytes of both sexes. By contrast, cholesteryl esters, diacylglycerols and triacylglycerols are significantly reduced in gABCG2-knockout gametocyte stages. We propose a role for gABCG2 in the regulation of gametocyte numbers and in the accumulation of neutral lipids, which are likely important for parasite development in the insect stages of the parasite life cycle.

Original language	English
Article number	4773
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5773
Publication status	Published - 2014

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abstract = "ATP-binding cassette (ABC) transporters serve a variety of physiological functions as well as play key roles in drug resistance. The genome of the human malaria parasite, Plasmodium falciparum, encodes multiple members of this family, one of which, gABCG2, is transcribed predominantly in the gametocyte stage. Here we use gene deletion and tagging to investigate the expression, localization and function of gABCG2. The protein is found in a single dot-like lipid-rich structure within female, but not male, gametocytes. gABCG2-knockout cell lines produce more gametocytes of both sexes. By contrast, cholesteryl esters, diacylglycerols and triacylglycerols are significantly reduced in gABCG2-knockout gametocyte stages. We propose a role for gABCG2 in the regulation of gametocyte numbers and in the accumulation of neutral lipids, which are likely important for parasite development in the insect stages of the parasite life cycle.",

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AU - Tran, Phuong N.

AU - Brown, Simon H.J.

AU - Mitchell, Todd W.

AU - Matuschewski, Kai

AU - McMillan, Paul J.

AU - Kirk, Kiaran

AU - Dixon, Matthew W.A.

AU - Maier, Alexander G.

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AB - ATP-binding cassette (ABC) transporters serve a variety of physiological functions as well as play key roles in drug resistance. The genome of the human malaria parasite, Plasmodium falciparum, encodes multiple members of this family, one of which, gABCG2, is transcribed predominantly in the gametocyte stage. Here we use gene deletion and tagging to investigate the expression, localization and function of gABCG2. The protein is found in a single dot-like lipid-rich structure within female, but not male, gametocytes. gABCG2-knockout cell lines produce more gametocytes of both sexes. By contrast, cholesteryl esters, diacylglycerols and triacylglycerols are significantly reduced in gABCG2-knockout gametocyte stages. We propose a role for gABCG2 in the regulation of gametocyte numbers and in the accumulation of neutral lipids, which are likely important for parasite development in the insect stages of the parasite life cycle.

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A female gametocyte-specific ABC transporter plays a role in lipid metabolism in the malaria parasite

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