title: Molecular characterization of a broad selectivity neutral solute channel.
abstract: In all living cells, coordination of solute and water movement across cell membranes is of critical importance for osmotic balance. The current concept is that these processes are of distinct biophysical nature. Here we report the expression cloning of a liver cDNA encoding a unique promiscuous solute channel (AQP9) that confers high permeability for both solutes and water. AQP9 mediates passage of a wide variety of non-charged solutes including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercury-sensitive manner, whereas amino acids, cyclic sugars, Na+, K+, Cl-, and deprotonated monocarboxylates are excluded. The properties of AQP9 define a new evolutionary branch of the major intrinsic protein family of aquaporin proteins and describe a previously unknown mechanism by which a large variety of solutes and water can pass through a single pore, enabling rapid cellular uptake or exit of metabolites with minimal osmotic perturbation.
authors.affiliation: Renal Division, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tsukaguchi
authors.forename: C
authors.initials: C
authors.lastname: Shayakul
authors.forename: U V
authors.initials: UV
authors.lastname: Berger
authors.forename: B
authors.initials: B
authors.lastname: Mackenzie
authors.forename: S
authors.initials: S
authors.lastname: Devidas
authors.forename: W B
authors.initials: WB
authors.lastname: Guggino
authors.forename: A N
authors.initials: AN
authors.lastname: van Hoek
authors.forename: M A
authors.initials: MA
authors.lastname: Hediger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051398:Aquaporin 1; D051400:Aquaporin 3; D020346:Aquaporins; D003001:Cloning, Molecular; D005260:Female; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D009994:Osmolar Concentration; D010693:Phloretin / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014982:Xenopus laevis
chemical_list: C496022:Aqp1 protein, rat; C496029:Aqp3 protein, rat; C491637:Aqp9 protein, rat; D020346:Aquaporins; D007473:Ion Channels; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051398:Aquaporin 1; D051400:Aquaporin 3; D010693:Phloretin