Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei.
The malaria parasite can use host plasma glycerol for lipid biosynthesis and membrane biogenesis during the asexual intraerythrocytic development. The molecular basis for glycerol uptake into the parasite is undefined. We hypothesize that the Plasmodium aquaglyceroporin provides the pathway for glycerol uptake into the malaria parasite. To test this hypothesis, we identified the orthologue of Plasmodium falciparum aquaglyceroporin (PfAQP) in the rodent malaria parasite, Plasmodium berghei (PbAQP), and examined the biological role of PbAQP by performing a targeted deletion of the PbAQP gene. PbAQP and PfAQP are 62% identical in sequence. In contrast to the canonical NPA (Asn-Pro-Ala) motifs in most aquaporins, the PbAQP has NLA (Asn-Leu-Ala) and NPS (Asn-Leu-Ser) in those positions. PbAQP expressed in Xenopus oocytes was permeable to water and glycerol, suggesting that PbAQP is an aquaglyceroporin. In P. berghei, PbAQP was localized to the parasite plasma membrane. The PbAQP-null parasites were viable; however, they were highly deficient in glycerol transport. In addition, they proliferated more slowly compared with the WT parasites, and mice infected with PbAQP-null parasites survived longer. Taken together, these findings suggest that PbAQP provides the pathway for the entry of glycerol into P. berghei and contributes to the growth of the parasite during the asexual intraerythrocytic stages of infection. In conclusion, we demonstrate here that PbAQP plays an important role in the blood-stage development of the rodent malaria parasite during infection in mice and could be added to the list of targets for the design of antimalarial drugs.
Promeneur
Dominique
D
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA. d.promeneur@cellbio.duke.edu
Liu
Yangjian
Y
Maciel
Jorge
J
Agre
Peter
P
King
Landon S
LS
Kumar
Nirbhay
N
D000595:Amino Acid Sequence; D000818:Animals; D051397:Aquaglyceroporins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport; D004912:Erythrocytes / Q000469:parasitology*; D005990:Glycerol / Q000378:metabolism; D051379:Mice; D016296:Mutagenesis; D010962:Plasmodium berghei / Q000737:chemistry* / Q000254:growth & development / Q000472:pathogenicity; D015800:Protozoan Proteins
D051397:Aquaglyceroporins; D015800:Protozoan Proteins; D005990:Glycerol