PUBLICATION

Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis

Authors
Angers, M., Uldry, M., Kong, D., Gimble, J.M., and Jetten, A.M.
ID
ZDB-PUB-090904-1
Date
2008
Source
The Biochemical journal   416(3): 347-355 (Journal)
Registered Authors
Keywords
β-adrenergic receptor (βAR), brown adipose tissue (BAT), permease, symporter, thermogenesis
MeSH Terms
  • Acclimatization/physiology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Symporters/genetics
  • Symporters/metabolism
  • Receptors, Thyroid Hormone/genetics
  • Receptors, Thyroid Hormone/metabolism
  • Receptors, Retinoic Acid/genetics
  • Receptors, Retinoic Acid/metabolism
  • Gene Expression Regulation
  • Humans
  • Fasting*
  • Mice, Inbred C57BL
  • Mice
  • Sequence Alignment
  • Adipose Tissue, Brown/metabolism*
  • Tissue Distribution
  • Receptors, Adrenergic, beta/genetics
  • Receptors, Adrenergic, beta/metabolism
  • Mice, Knockout
  • Protein Isoforms/classification
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Animals
  • Cell Line
  • Base Sequence
  • Thermogenesis/physiology*
  • Molecular Sequence Data
  • Signal Transduction/physiology
  • Membrane Transport Proteins/classification
  • Membrane Transport Proteins/genetics
  • Membrane Transport Proteins/metabolism*
  • Amino Acid Sequence
  • Oligonucleotide Array Sequence Analysis
  • Circadian Rhythm
  • Phylogeny
PubMed
18694395 Full text @ Biochem. J.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping