Aquaglyceroporins form a subfamily of the aquaporin water channel family-transporting water, glycerol and urea. Human red blood cells [RBCs] contain the aquaglyceroporin AQP3;mouse RBCs contain AQP9. Plasmodia causing malaria contain aquaglyceroporins -- P. falciparum causes human malaria and expresses PfAQP;P. berghei causes mouse malaria and expresses PbAQP. Glycerol is used by the intracellular malaria parasite [merozoite] for production of glycerolipids. Import of glycerol requires transport of the solute across three membranes - the RBC plasma membrane [PM], the parasitophorous vacuolar membrane [PVM], and the plasmodia plasma membrane [PPM]. We hypothesize that aquaglyceroporins are involved in malarial infection and may provide a new pathway of potential therapeutic importance.
Aim I. To understand the contribution of aquaglyceroporins to glycerol transport by RBC membranes, the copy numbers will be determined for AQP3 in human and AQP9 in mouse RBCs. We will also compare the water, glycerol, and urea permeability of aquaglyceroporin null RBCs to wildtype cells.
Aim II. The biophysical functions of aquaglyceroporin PbAQP from P. berghei will be characterized. In addition the localization and expression of PbAQP will be defined during the life cycle of the organism.
Aim III. Aquaglyceroporin null cells will allow us to understand the role of these channels in malarial infection. The pathogenicity of PbAQP null P. berghei will be compared to that of wildtype parasites. The role of AQP9 will be determined by comparing the parasitemia of wildtype mice to that of AQP9 null mice. The mouse model of malaria will also be evaluated in the insect stages of Plasmodium by studying the expression of PbAQP in the insect and the effect of PbAQP disruption on the proliferation of P. berghei in the mosquito and the transmission of P. berghei from the mosquito to the mouse.
Aim I V. Investigation of the human malaria parasite, P. falciparum, will be crucial for understanding roles for aquaglyceroporins in human malarial infection. Human RBCs will be infected with PfAQP null or wildtype P. falciparum, and the parasitemia compared. To determine the role of the human RBC aquaglyceroporins in malaria, parasitemia of wildtype RBCs will be compared to AQP3 null RBCs. Malaria is a major cause of disease and death of children in many underdeveloped countries. The parasites causing malaria invade red blood cells and multiply, causing massive cellular destruction. The goal of this application is to define the pathway for uptake of the nutrient glycerol by red blood cells and malaria parasites, with hope that this may reveal new avenues for prevention or treatment of malaria.
|Liu, Kun; Tsujimoto, Hitoshi; Huang, Yuzheng et al. (2016) Aquaglyceroporin function in the malaria mosquito Anopheles gambiae. Biol Cell 108:294-305|
|Huang, Yuzheng; Li, Wei; Lu, Wuguang et al. (2016) Cloning and in vitro characterization of a Schistosoma japonicum aquaglyceroporin that functions in osmoregulation. Sci Rep 6:35030|
|Liu, Kun; Dong, Yuemei; Huang, Yuzheng et al. (2013) Impact of trehalose transporter knockdown on Anopheles gambiae stress adaptation and susceptibility to Plasmodium falciparum infection. Proc Natl Acad Sci U S A 110:17504-9|
|Promeneur, Dominique; Lunde, Lisa Kristina; Amiry-Moghaddam, Mahmood et al. (2013) Protective role of brain water channel AQP4 in murine cerebral malaria. Proc Natl Acad Sci U S A 110:1035-40|
|Tsujimoto, Hitoshi; Liu, Kun; Linser, Paul J et al. (2013) Organ-specific splice variants of aquaporin water channel AgAQP1 in the malaria vector Anopheles gambiae. PLoS One 8:e75888|
|Liu, Kun; Tsujimoto, Hitoshi; Cha, Sung-Jae et al. (2011) Aquaporin water channel AgAQP1 in the malaria vector mosquito Anopheles gambiae during blood feeding and humidity adaptation. Proc Natl Acad Sci U S A 108:6062-6|
|Potter, James J; Koteish, Ayman; Hamilton, James et al. (2011) Effects of acetaldehyde on hepatocyte glycerol uptake and cell size: implication of aquaporin 9. Alcohol Clin Exp Res 35:939-45|
|Mharakurwa, Sungano; Kumwenda, Taida; Mkulama, Mtawa A P et al. (2011) Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes. Proc Natl Acad Sci U S A 108:18796-801|
|Rash, J E (2010) Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system. Neuroscience 168:982-1008|
|Liu, Yangjian; Song, Linhua; Wang, Yiding et al. (2009) Osteoclast differentiation and function in aquaglyceroporin AQP9-null mice. Biol Cell 101:133-40|
Showing the most recent 10 out of 79 publications