title: Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis.
abstract: This study describes the identification of Mfsd2a (major facilitator superfamily domain-containing protein 2a), a novel mammalian major facilitator superfamily domain-containing protein, and an additional closely related protein, Mfsd2b. Most intron/exon junctions are conserved between the two genes, suggesting that they are derived from a common ancestor. Mfsd2a and Mfsd2b share a 12 transmembrane alpha-helical domain structure that bears greatest similarity to that of the bacterial Na(+)/melibiose symporters. Confocal microscopy demonstrated that Mfsd2a localizes to the endoplasmic reticulum. Mfsd2a is expressed in many tissues and is highly induced in liver and BAT (brown adipose tissue) during fasting. Mfsd2a displays an oscillatory expression profile in BAT and liver, consistent with a circadian rhythm. Although the basal level of Mfsd2a expression is relatively low in mouse BAT, it is greatly induced during cold-induced thermogenesis and after treatment with betaAR (beta-adrenergic receptor) agonists. This induction is totally abolished in beta-less (betaAR-deficient) mice. These findings indicate that Mfsd2a is greatly up-regulated in BAT during thermogenesis and that its induction is controlled by the betaAR signalling pathway. The observed induction of Mfsd2a expression in cultured BAT cells by dibutyryl-cAMP is in agreement with this conclusion. The present study suggests that Mfsd2a plays a role in adaptive thermogenesis.
authors.affiliation: Cell Biology Section, LRB, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Angers
authors.forename: Marc
authors.initials: M
authors.lastname: Uldry
authors.forename: Dong
authors.initials: D
authors.lastname: Kong
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.forename: Anton M
authors.initials: AM
authors.lastname: Jetten
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002940:Circadian Rhythm; D005215:Fasting; D005786:Gene Expression Regulation; D006801:Humans; D026901:Membrane Transport Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D026901:Membrane Transport Proteins; C534136:Mfsd2a protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020033:Protein Isoforms; C539900:RORC protein, human; D011943:Receptors, Adrenergic, beta; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D027981:Symporters; C021548:melibiose permease