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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology
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The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology

机译：脂肪营养不良蛋白脂蛋白存在于内质网脂质液滴连接处，对液滴形态很重要

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Lipodystrophy is a disorder characterized by a loss of adipose tissue often accompanied by severe hypertriglyceridemia, insulin resistance, diabetes, and fatty liver. It can be inherited or acquired. The most severe inherited form is Berardinelli-Seip Congenital Lipodystrophy Type 2, associated with mutations in the BSCL2 gene. BSCL2 encodes seipin, the function of which has been entirely unknown. We now report the identification of yeast B5CL2/seipin through a screen to detect genes important for lipid droplet morphology. The absence of yeast seipin results in irregular lipid droplets often clustered alongside proliferated endoplasmic reticulum (ER); giant lipid droplets are also seen. Many small irregular lipid droplets are also apparent in fibroblasts from a BSCL2 patient. Human seipin can functionally replace yeast seipin, but a missense mutation in human seipin that causes lipodystrophy, or corresponding mutations in the yeast gene, render them unable to complement. Yeast seipin is localized in the ER, where it forms puncta. Almost all lipid droplets appear to be on the ER, and seipin is found at these junctions. Therefore, we hypothesize that seipin is important for droplet maintenance and perhaps assembly. In addition to detecting seipin, the screen identified 58 other genes whose deletions cause aberrant lipid droplets, including 2 genes encoding proteins known to activate lipin, a lipodystrophy locus in mice, and 16 other genes that are involved in endosomal-lysosomal trafficking. The genes identified in our screen should be of value in understanding the pathway of lipid droplet biogenesis and maintenance and the cause of some lipodystrophies.
机译：血脂异常是一种以脂肪组织减少为特征的疾病，通常伴有严重的高甘油三酯血症，胰岛素抵抗，糖尿病和脂肪肝。它可以被继承或获取。最严重的遗传形式是Berardinelli-Seip先天性脂肪营养不良2型，与BSCL2基因的突变有关。 BSCL2编码seipin，其功能完全未知。现在，我们通过筛查报告酵母B5CL2 / seipin的鉴定，以检测对脂滴形态重要的基因。缺乏酵母seipin会导致不规则的脂滴，通常与增生的内质网（ER）聚集在一起。还可以看到巨大的脂质滴。在BSCL2患者的成纤维细胞中，许多小的不规则脂质滴也很明显。人脂蛋白可以在功能上替代酵母脂蛋白，但是人脂蛋白的错义突变会导致脂肪营养不良或酵母基因中的相应突变，使其无法互补。酵母seipin定位于ER中，在此处形成点状。几乎所有脂滴似乎都在ER上，并且在这些连接处发现了seipin。因此，我们假设seipin对维持液滴和组装很重要。除了检测脂蛋白，该筛选还鉴定了其他58个基因的缺失，这些基因的缺失会导致脂质滴的异常，其中包括2个编码激活脂蛋白的蛋白质的基因，一个小鼠脂肪营养不良的基因座，以及其他16个与内体-溶酶体运输有关的基因。在我们的筛查中鉴定出的基因对于理解脂质小滴的生物发生和维持的途径以及某些脂肪营养不良的原因具有重要的价值。

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