Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence

Abstract

Human and rodent erythrocytes are known to be highly permeable to glycerol. Aquaglyceroporin aquaporin (AQP)3 is the major glycerol channel in human and rat erythrocytes. However, AQP3 expression has not been observed in mouse erythrocytes. Here we report the presence of an aquaglyceroporin, AQP9, in mouse erythrocytes. AQP9 levels rise as reticulocytes mature into erythrocytes and as neonatal pups develop into adult mice. Mice bearing targeted disruption of both alleles encoding AQP9 have erythrocytes that appear morphologically normal. Compared with WT cells, erythrocytes from AQP9-null mice are defective in rapid glycerol transport across the cell membrane when measured by osmotic lysis, [ 14 C]glycerol uptake, or stopped-flow light scattering. In contrast, the water and urea permeabilities are intact. Although the physiological role of glycerol in the normal function of erythrocytes is not clear, plasma glycerol is an important substrate for lipid biosynthesis of intraerythrocytic malarial parasites. AQP9-null mice at the age of 4 months infected with Plasmodium berghei survive longer during the initial phase of infection compared with WT mice. We conclude that AQP9 is the major glycerol channel in mouse erythrocytes and suggest that this transport pathway may contribute to the virulence of intraerythrocytic stages of malarial infection.Plasmodium berghei ͉ aquaglyceroporin A quaglyceroporins are transmembrane proteins belonging to the aquaporin (AQP) water channel family (1). Aquaglyceroporins are the only known glycerol channels in mammalian cells. Among 13 identified mammalian aquaporins, AQP3, AQP7, AQP9, and AQP10 represent the aquaglyceroporin subfamily on the basis of their amino acid sequences and solute permeabilities (1). Aquaglyceroporins are also permeable to urea and water when expressed in Xenopus laevis oocytes (1).The first defined water channel, AQP1, was discovered in human erythrocytes (2). The high expression and water permeability of AQP1 in erythrocytes led to the hypothesis that AQP1 is important in adaptation to dramatic osmolarity changes in the circulation (2). In addition to high water permeability, human and rodent erythrocytes are known to be highly permeable to urea and glycerol (3). AQP3 has been identified as the main channel for glycerol transport in human and rat erythrocytes (4). AQP3 has not been detected in mouse erythrocytes, and the glycerol permeability of mouse erythrocytes from AQP3 knockout mice has been shown to not be affected by gene deletion (5). We revisited this question and detected AQP9 expression in mouse erythrocytes. By using AQP9-null mice, we provide evidence that AQP9 is the major pathway for glycerol transport in mouse erythrocytes.The physiological role of aquaglyceroporins in erythrocytes is still not clear. However, recent studies indicate that aquaglyceroporins AQP7 and AQP9 participate in metabolism. Under fasting conditions, up-regulated AQP7 expression in adipocytes facilitates the release of glycerol, which can then be transported through the ...

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

“…Immunobloting with anti-rAQP3 revealed that AQP3 is abundantly 12 expressed in hRBC ( Figure 3B). In this sample the AQP3 antibody recognized a broad band at ~ 40-50 kDa, which was reduced to 29 kDa after PNGase F treatment, indicating the expression of glycosylated AQP3 in hRBC as previously described [15,26]. In bRBC two faint bands at ~ 40-50 kDa were detected.…”

“…Absence of AQP3 has also been described in mouse erythrocytes [15], where another aquaglyceroporin isoform (AQP9) plays the role of glycerol channel maintaining the red cells highly permeable to glycerol [26]. The reason why bovine red cells do not contain glycerol channels is not obvious.…”

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

“…This hypothesis had previously been formulated for ABO and FUT2 (Greenwell 1997;Hill 2006;Casanova and Abel 2007), while in the case of GYPC, DARC, and SLC4A1 the ability of specific alleles to modulate infection susceptibility has been demonstrated for malaria (Moulds and Moulds 2000). Also, in the case of AQP3, modulation of malaria severity can be hypothesized since AQP3 represents the major channel for glycerol transport in human erythrocytes (Roudier et al 2002), and mice knockout for Aqp9, a related glycerol transporting aquaporin, display increased survival to P. berghei (Liu et al 2007). One possibility to explain the observed associations is that pathogen richness has co-varied with malaria prevalence and that nucleotide variations, even different from those previously reported to confer resistance in SLC4A1 and GYPC, affect Plasmodium entry, spread, or rosetting.…”

Expression of the Water Channel Protein Aquaporin-9 in Human Astrocytic Tumours: Correlation with Pathological Grade

“…1,2 It has previously been shown that the expression of aquaporin-9 (AQP9) changes in some pathological situations. 3,4 In this study the expression of AQP9 and its correlation with pathological grade was investigated in 100 human brain astrocytic tumours.…”