title: Increased water flux induced by an aquaporin-1/carbonic anhydrase II interaction.
abstract: Aquaporin-1 (AQP1) enables greatly enhanced water flux across plasma membranes. The cytosolic carboxy terminus of AQP1 has two acidic motifs homologous to known carbonic anhydrase II (CAII) binding sequences. CAII colocalizes with AQP1 in the renal proximal tubule. Expression of AQP1 with CAII in Xenopus oocytes or mammalian cells increased water flux relative to AQP1 expression alone. This required the amino-terminal sequence of CAII, a region that binds other transport proteins. Expression of catalytically inactive CAII failed to increase water flux through AQP1. Proximity ligation assays revealed close association of CAII and AQP1, an effect requiring the second acidic cluster of AQP1. This motif was also necessary for CAII to increase AQP1-mediated water flux. Red blood cell ghosts resealed with CAII demonstrated increased osmotic water permeability compared with ghosts resealed with albumin. Water flux across renal cortical membrane vesicles, measured by stopped-flow light scattering, was reduced in CAII-deficient mice compared with wild-type mice. These data are consistent with CAII increasing water conductance through AQP1 by a physical interaction between the two proteins.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Vilas
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Devishree
authors.initials: D
authors.lastname: Krishnan
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Sampath Kumar
authors.initials: SK
authors.lastname: Loganathan
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Darpan
authors.initials: D
authors.lastname: Malhotra
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Megan Rachele
authors.initials: MR
authors.lastname: Beggs
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70121 Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gena
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70121 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calamita
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Saarland University, D-66424 Homburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Saarland University, D-66424 Homburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70121 Bari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Tamma
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, AB T6G 1C9, Canada Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada.
authors.forename: Joseph Roman
authors.initials: JR
authors.lastname: Casey
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada Membrane Protein Disease Research Group, University of Alberta, Edmonton, AB T6G 1C9, Canada Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada todd2@ualberta.ca.
authors.forename: Robert Todd
authors.initials: RT
authors.lastname: Alexander
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014867:Water / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C496020:AQP1 protein, human; D014867:Water; D051398:Aquaporin 1; D024402:Carbonic Anhydrase II