Aquaglyceroporins in erythrocytes, malarial parasites, and osteoclasts

Aquaglyceroporins are members of the aquaporin water channel family that transport water, glycerol, and urea. These channels are known to be involved in glycerol metabolism. However, the physiological roles of these aquaglyceroporins are not clear. This dissertation summarizes studies on the physiological roles of aquaglyceroporins in erythrocytes, malarial parasites, and osteoclasts.; Aquaglyceroporin AQP3 is the major glycerol channel in human and rat erythrocytes but not in mouse erythrocytes. We detected an aquaglyceroporin, AQP9, in mouse erythrocytes. Compared to wild type cells, erythrocytes from AQP9 deficient mice are defective in rapid glycerol transport across the cell membrane, whereas the water and urea permeabilities are intact. While the physiological role of glycerol in the normal function of erythrocytes is not clear, plasma glycerol is an important substrate for lipid biosynthesis in intraerythrocytic malarial parasites. AQP9 null mice infected with Plasmodium berghei, the mouse malarial parasite, survive longer during the initial phase of infection compared to wild type mice. We conclude that AQP9 is the glycerol channel in mouse erythrocytes and suggest that this transport pathway contributes to the virulence of the intraerythrocytic stages of Plasmodium.; An aquaglyceroporin in P. berghei, PbAQP, was identified and hypothesized to be the major pathway for glycerol uptake from erythrocytes into the mouse malarial parasite for rapid lipid biosynthesis. Expression of PbAQP in Xenopus oocytes revealed that PbAQP is permeable to water, glycerol and urea. PbAQP deficient parasites proliferate more slowly than wild-type parasites. Mice infected with PbAQP null parasites survive longer than mice infected with wild type parasites. This study reveals that the glycerol uptake pathway through an aquaglyceroporin contributes to the growth of P. berghei during infection in mice.; An increase in expression of aquaglyceroporin AQP9 was detected during differentiation of mouse macrophages into osteoclasts. There was no difference between wild type and AQP9 null osteoclasts in morphology or bone absorption activity. The density and structure of long bones from AQP9 null mice were similar to those from wild type mice. Our data suggest that AQP9 is not essential for osteoclasts under normal physiological conditions but may be important for osteoclast function under stress.