Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids.
Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids.
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DOI：
10.1083/jcb.149.3.707
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发表时间：
2000-05-01
期刊：
影响因子：
--
通讯作者：
Jacobsson A
中科院分区：
文献类型：
--
作者：
Tvrdik P;Westerberg R;Silve S;Asadi A;Jakobsson A;Cannon B;Loison G;Jacobsson A
尽管微粒体脂肪酸延长的生理意义是普遍赞赏的，但其分子性质知之甚少。在这里，我们描述了一个新的小鼠基因家族编码的非常长链脂肪酸的合成中所涉及的组件的组织特异性调节。Ssc 1基因似乎是普遍表达的，而Ssc 2和Ssc 30显示出有限的表达模式。它们的翻译产物都是具有5个跨膜结构域的完整膜蛋白。通过补充同源酵母突变体，我们发现Ssc 1可以拯救缺乏合成蜡酸（C26：0）能力的sur 4/elo 3突变体中的正常鞘脂合成。类似地，Fen 30恢复了fen 1/elo 2突变体的表型，该突变体具有C20-C24范围内的脂肪酸水平降低。此外，我们发现，Ssc 1 mRNA水平显着降低，在大脑中的髓鞘缺陷的小鼠突变体已知具有非常低的脂肪酸链延长活性。相反，在棕色脂肪募集过程中，显著诱导的EST 30表达与延长活性升高相一致。我们的研究结果强烈暗示这个新的哺乳动物基因家族在组织特异性合成的非常长链脂肪酸和鞘脂。
Whereas the physiological significance of microsomal fatty acid elongation is generally appreciated, its molecular nature is poorly understood. Here, we describe tissue-specific regulation of a novel mouse gene family encoding components implicated in the synthesis of very long chain fatty acids. The Ssc1 gene appears to be ubiquitously expressed, whereas Ssc2 and Cig30 show a restricted expression pattern. Their translation products are all integral membrane proteins with five putative transmembrane domains. By complementing the homologous yeast mutants, we found that Ssc1 could rescue normal sphingolipid synthesis in the sur4/elo3 mutant lacking the ability to synthesize cerotic acid (C26:0). Similarly, Cig30 reverted the phenotype of the fen1/elo2 mutant that has reduced levels of fatty acids in the C20–C24 range. Further, we show that Ssc1 mRNA levels were markedly decreased in the brains of myelin-deficient mouse mutants known to have very low fatty acid chain elongation activity. Conversely, the dramatic induction of Cig30 expression during brown fat recruitment coincided with elevated elongation activity. Our results strongly implicate this new mammalian gene family in tissue-specific synthesis of very long chain fatty acids and sphingolipids.
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DOI：
10.2170/jjphysiol.40.57
发表时间：
1990-01-01
期刊：
JAPANESE JOURNAL OF PHYSIOLOGY
影响因子：
--
作者：
KUROSHIMA, A;OHNO, T
通讯作者：
OHNO, T
影响因子：
14.9
作者：
DEVEREUX, J;HAEBERLI, P;SMITHIES, O
通讯作者：
SMITHIES, O
ELO2 和 ELO3 是酿酒酵母 ELO1 基因的同源物，它们在脂肪酸伸长过程中发挥作用，并且是鞘脂形成所必需的
影响因子：
4.8
作者：
Oh, CS;Toke, DA;Martin, CE
通讯作者：
Martin, CE
影响因子：
11.6
作者：
Millar, AA;Clemens, S;Kunst, L
通讯作者：
Kunst, L
影响因子：
4.1
作者：
CLARKE, NG;DAWSON, RMC
通讯作者：
DAWSON, RMC