title: Yeast aquaglyceroporins use the transmembrane core to restrict glycerol transport.
abstract: Aquaglyceroporins are transmembrane proteins belonging to the family of aquaporins, which facilitate the passage of specific uncharged solutes across membranes of cells. The yeast aquaglyceroporin Fps1 is important for osmoadaptation by regulating intracellular glycerol levels during changes in external osmolarity. Upon high osmolarity conditions, yeast accumulates glycerol by increased production of the osmolyte and by restricting glycerol efflux through Fps1. The extended cytosolic termini of Fps1 contain short domains that are important for regulating glycerol flux through the channel. Here we show that the transmembrane core of the protein plays an equally important role. The evidence is based on results from an intragenic suppressor mutation screen and domain swapping between the regulated variant of Fps1 from Saccharomyces cerevisiae and the hyperactive Fps1 ortholog from Ashbya gossypii. This suggests a novel mechanism for regulation of glycerol flux in yeast, where the termini alone are not sufficient to restrict Fps1 transport. We propose that glycerol flux through the channel is regulated by interplay between the transmembrane helices and the termini. This mechanism enables yeast cells to fine-tune intracellular glycerol levels at a wide range of extracellular osmolarities.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-40530 Gothenburg, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Geijer
authors.forename: Doryaneh
authors.initials: D
authors.lastname: Ahmadpour
authors.forename: Madelene
authors.initials: M
authors.lastname: Palmgren
authors.forename: Caroline
authors.initials: C
authors.lastname: Filipsson
authors.forename: Dagmara Medrala
authors.initials: DM
authors.lastname: Klein
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Tamás
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohmann
authors.forename: Karin
authors.initials: K
authors.lastname: Lindkvist-Petersson
mesh_terms: D000595:Amino Acid Sequence; D051397:Aquaglyceroporins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D001692:Biological Transport; D055169:Eremothecium / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D005990:Glycerol / Q000378:metabolism*; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009994:Osmolar Concentration; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012965:Sodium Chloride / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000235:genetics
chemical_list: D051397:Aquaglyceroporins; C093263:FPS1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D012965:Sodium Chloride; D005990:Glycerol; D005998:Glycine