Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis.
Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis.
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DOI：
10.1042/bj20080165
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发表时间：
2008-12-15
期刊：
影响因子：
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通讯作者：
Jetten AM
中科院分区：
文献类型：
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作者：
Angers M;Uldry M;Kong D;Gimble JM;Jetten AM
本研究描述了一种新的哺乳动物主要促进剂超家族结构域蛋白Mfsd2a的鉴定，以及另一种密切相关的蛋白Mfsd2b。大多数内含子/外显子连接在两个基因之间是保守的，这表明它们来自共同的祖先。Mfsd2a/b具有一个12跨膜的α-螺旋结构域结构，与细菌的Na+/Melibiose共转运蛋白的结构非常相似。共聚焦显微镜显示Mfsd2a定位于内质网。Mfsd2a在多种组织中表达，禁食时在肝脏和棕色脂肪组织(BAT)中高表达。Mfsd2a在蝙蝠和肝脏中显示出与昼夜节律一致的振荡表达谱。虽然BAT小鼠Mfsd2a的基础表达水平相对较低，但在冷诱导的生热过程中和β肾上腺素能受体(βAR)激动剂处理后，Mfsd2a的表达显著增加。这种诱导在βAR缺陷(β-Less)小鼠中完全取消。这些发现表明，Mfsd2a在产热过程中在BAT中显著上调，其诱导受βAR信号通路的控制。观察到二丁酰cAMP对培养的蝙蝠细胞Mfsd2a表达的诱导与此结论一致。我们的研究表明，Mfsd2a在适应性产热中起作用。
This study describes the identification of a novel mammalian major facilitator superfamily domain-containing protein, referred to as Mfsd2a, and an additional closely related protein, designated Mfsd2b. Most intron/exon junctions are conserved between the two genes suggesting that they are derived from a common ancestor. Mfsd2a/b share a 12 transmembrane α-helical domain structure that shows 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 brown adipose tissue (BAT) during fasting. Mfsd2a displays an oscillatory expression profile in BAT and liver consistent with a circadian rhythm. While the basal level of Mfsd2a expression is relatively low in BAT in mice, it is greatly induced during cold-induced thermogenesis and after treatment with β-adrenergic receptor (βAR) agonists. This induction is totally abolished in βAR-deficient (β-less) mice. These findings indicate that Mfsd2a is greatly up-regulated in BAT during thermogenesis and that its induction is controlled by the βAR signaling pathway. The observed induction of Mfsd2a expression in cultured BAT cells by dibutyryl-cAMP is in agreement with this conclusion. Our study suggests that Mfsd2a has a role in adaptive thermogenesis.