Intracellular Plasmodium aquaporin 2 is important for sporozoite production in the mosquito vector and malaria transmission

被引:0
|
作者
Bailey, Alexander J. [1 ]
Ukegbu, Chiamaka Valerie [1 ]
Giorgalli, Maria [1 ]
Besson, Tanguy Rene Balthazar [1 ]
Christophides, George K. [1 ]
Vlachou, Dina [1 ]
机构
[1] Imperial Coll London, Dept Life Sci, London SW72AZ, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
malaria parasite; mosquito vector; aquaporin; Plasmodium ookinete; oocyst development; TOXOPLASMA-GONDII; PARASITE; CHANNEL; AQUAGLYCEROPORIN; FALCIPARUM; SINGLE; DATABASE; BERGHEI;
D O I
10.1073/pnas.2304339120
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Malaria remains a devastating disease and, with current measures failing to control its transmission, there is a need for novel interventions. A family of proteins that have long been pursued as potential intervention targets are aquaporins, which are channels facilitating the movement of water and other solutes across membranes. We identify an aquaporin in malaria parasites and demonstrate that it is important for completion of Plasmodium development in the mosquito vector. Disruption of AQP2 in the human parasite Plasmodium falciparum and the rodent parasite Plasmodium berghei blocks sporozoite production inside oocysts established on mosquito midguts, greatly limiting parasite infection of salivary glands and transmission to a new host. In vivo epitope tagging of AQP2 in P. berghei, combined with immunofluorescence assays, reveals that the protein is localized in vesicle-like organelles found in the cytoplasm of gametocytes, ookinetes, and sporozoites. The number of these orga-nelles varies between individual parasites and lifecycle stages suggesting that they are likely part of a dynamic endomembrane system. Phylogenetic analysis confirms that AQP2 is unique to malaria and closely related parasites and most closely resembles intracellular aquaporins. Structure prediction analyses identify several unusual fea-tures, including a large accessory extracellular loop and an arginine-to- phenylalanine substitution in the selectivity filter principally determining pore function, a unique feature among known aquaporins. This in conjunction with the importance of AQP2 for malaria transmission suggests that AQP2 may be a fruitful target of antimalarial interventions.
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页数:9
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