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

Yangjian Liu, Dominique Promeneur, Aleksandra Rojek, Nirbhay Kumar, Jørgen Frøkiær, Søren Nielsen, Landon Stuart King, Peter C Agre, Jennifer M. Carbrey

Research output: Contribution to journalArticle

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, [14C]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 dear, 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.

LanguageEnglish (US)
Pages12560-12564
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number30
DOIs
StatePublished - Jul 24 2007

Fingerprint

Aquaporins
Glycerol
Virulence
Erythrocytes
Aquaglyceroporins
Aquaporin 3
Plasmodium berghei
Reticulocytes
Infection
Urea
Rodentia
Permeability
Parasites
Alleles
Cell Membrane
Lipids
Light
Water

Keywords

  • Aquaglyceroporin
  • Plasmodium berghei

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence. / Liu, Yangjian; Promeneur, Dominique; Rojek, Aleksandra; Kumar, Nirbhay; Frøkiær, Jørgen; Nielsen, Søren; King, Landon Stuart; Agre, Peter C; Carbrey, Jennifer M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 30, 24.07.2007, p. 12560-12564.

Research output: Contribution to journalArticle

Liu, Yangjian ; Promeneur, Dominique ; Rojek, Aleksandra ; Kumar, Nirbhay ; Frøkiær, Jørgen ; Nielsen, Søren ; King, Landon Stuart ; Agre, Peter C ; Carbrey, Jennifer M. / Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 30. pp. 12560-12564.
@article{a6278da6715f4613a56f18e5f5321b29,
title = "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, [14C]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 dear, 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.",
keywords = "Aquaglyceroporin, Plasmodium berghei",
author = "Yangjian Liu and Dominique Promeneur and Aleksandra Rojek and Nirbhay Kumar and J{\o}rgen Fr{\o}ki{\ae}r and S{\o}ren Nielsen and King, {Landon Stuart} and Agre, {Peter C} and Carbrey, {Jennifer M.}",
year = "2007",
month = "7",
day = "24",
doi = "10.1073/pnas.0705313104",
language = "English (US)",
volume = "104",
pages = "12560--12564",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "30",

}

TY - JOUR

T1 - Aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence

AU - Liu, Yangjian

AU - Promeneur, Dominique

AU - Rojek, Aleksandra

AU - Kumar, Nirbhay

AU - Frøkiær, Jørgen

AU - Nielsen, Søren

AU - King, Landon Stuart

AU - Agre, Peter C

AU - Carbrey, Jennifer M.

PY - 2007/7/24

Y1 - 2007/7/24

N2 - 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, [14C]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 dear, 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.

AB - 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, [14C]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 dear, 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.

KW - Aquaglyceroporin

KW - Plasmodium berghei

UR - http://www.scopus.com/inward/record.url?scp=34547641418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547641418&partnerID=8YFLogxK

U2 - 10.1073/pnas.0705313104

DO - 10.1073/pnas.0705313104

M3 - Article

VL - 104

SP - 12560

EP - 12564

JO - Proceedings of the National Academy of Sciences of the United States of America

T2 - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 30

ER -