title: The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake.
abstract: Membrane-bound solute carriers (SLCs) are essential as they maintain several physiological functions, such as nutrient uptake, ion transport and waste removal. The SLC family comprise about 400 transporters, and we have identified two new putative family members, major facilitator superfamily domain containing 1 (MFSD1) and 3 (MFSD3). They cluster phylogenetically with SLCs of MFS type, and both proteins are conserved in chordates, while MFSD1 is also found in fruit fly. Based on homology modelling, we predict 12 transmembrane regions, a common feature for MFS transporters. The genes are expressed in abundance in mice, with specific protein staining along the plasma membrane in neurons. Depriving mouse embryonic primary cortex cells of amino acids resulted in upregulation of Mfsd1, whereas Mfsd3 is unaltered. Furthermore, in vivo, Mfsd1 and Mfsd3 are downregulated in anterior brain sections in mice subjected to starvation, while upregulated specifically in brainstem. Mfsd3 is also attenuated in cerebellum after starvation. In mice raised on high-fat diet, Mfsd1 was specifically downregulated in brainstem and hypothalamus, while Mfsd3 was reduced consistently throughout the brain.
authors.affiliation: Unit of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden. Emelie.Perland@neuro.uu.se.|Unit of Molecular Neuropharmacology, Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden. Emelie.Perland@neuro.uu.se.
authors.forename: Emelie
authors.initials: E
authors.lastname: Perland
authors.affiliation: Unit of Molecular Neuropharmacology, Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden.
authors.forename: Sofie V
authors.initials: SV
authors.lastname: Hellsten
authors.affiliation: Unit of Molecular Neuropharmacology, Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden.
authors.forename: Emilia
authors.initials: E
authors.lastname: Lekholm
authors.affiliation: Unit of Molecular Neuropharmacology, Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden.
authors.forename: Mikaela M
authors.initials: MM
authors.lastname: Eriksson
authors.affiliation: Unit of Molecular Neuropharmacology, Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Arapi
authors.affiliation: Unit of Molecular Neuropharmacology, Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
mesh_terms: D000596:Amino Acids / Q000172:deficiency; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D017124:Conserved Sequence; D059305:Diet, High-Fat; D005260:Female; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010802:Phylogeny; D000072417:Protein Domains; D013217:Starvation
chemical_list: D000596:Amino Acids; C000620844:MFSD1 protein, mouse; C000620845:MFSD3 protein, mouse; D026901:Membrane Transport Proteins
keywords: MFSD1; MFSD3; Protein expression; SLC