title: Identification of key residues involved in Si transport by the aquaglyceroporins.
abstract: We recently demonstrated that the aquaglyceroporins (AQGPs) could act as potent transporters for orthosilicic acid (H4SiO4). Although interesting, this finding raised the question of whether water and H4SiO4, the transportable form of Si, permeate AQGPs by interacting with the same region of the pore, especially in view of the difference in molecular radius between the two substrates. Here, our goal was to identify residues that endow the AQGPs with the ability to facilitate Si diffusion by examining the transport characteristics of mutants in which residues were interchanged between a water-permeable but Si-impermeable channel (aquaporin 1 [AQP1]) and a Si-permeable but water-impermeable channel (AQP10). Our results indicate that the composition of the arginine filter (XX/R), known to include three residues that play an important role in water transport, may also be involved in Si selectivity. Interchanging the identities of the nonarginine residues within this filter causes Si transport to increase by approximately sevenfold in AQP1 and to decrease by approximately threefold in AQP10, whereas water transport and channel expression remain unaffected. Our results further indicate that two additional residues in the AQP arginine filter may be involved in substrate selectivity: replacing one of the residues has a profound effect on water permeability, and replacing the other has a profound effect on Si permeability. This study has thus led to the identification of residues that could play a key role in Si transport by the AQGPs and shown that substrate selectivity is likely ensured by more than one checkpoint within or near the pore.
authors.affiliation: Nephrology Research Group, Department of Medicine, Laval University, L'Hôtel-Dieu de Québec Hospital, Québec, Québec G1R 2J6, Canada.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Carpentier
authors.affiliation: Nephrology Research Group, Department of Medicine, Laval University, L'Hôtel-Dieu de Québec Hospital, Québec, Québec G1R 2J6, Canada.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Garneau
authors.affiliation: Nephrology Research Group, Department of Medicine, Laval University, L'Hôtel-Dieu de Québec Hospital, Québec, Québec G1R 2J6, Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Marcoux
authors.affiliation: Nephrology Research Group, Department of Medicine, Laval University, L'Hôtel-Dieu de Québec Hospital, Québec, Québec G1R 2J6, Canada.
authors.forename: Micheline
authors.initials: M
authors.lastname: Noël
authors.affiliation: Nephrology Research Group, Department of Medicine, Laval University, L'Hôtel-Dieu de Québec Hospital, Québec, Québec G1R 2J6, Canada.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Frenette-Cotton
authors.affiliation: Nephrology Research Group, Department of Medicine, Laval University, L'Hôtel-Dieu de Québec Hospital, Québec, Québec G1R 2J6, Canada paul.isenring@crhdq.ulaval.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Isenring
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051397:Aquaglyceroporins / Q000378:metabolism*; D020346:Aquaporins / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology*; D004058:Diffusion; D026901:Membrane Transport Proteins / Q000378:metabolism; D010539:Permeability; D012825:Silicon / Q000378:metabolism*; D014867:Water / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism
chemical_list: D051397:Aquaglyceroporins; D020346:Aquaporins; D026901:Membrane Transport Proteins; D014867:Water; D001120:Arginine; D012825:Silicon