Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Rowett Institute and Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Cells. 2019 Mar 21;8(3):268. doi: 10.3390/cells8030268.
Seipin (BSCL2/SPG17) is a key factor in lipid droplet (LD) biology, and its dysfunction results in severe pathologies, including the fat storage disease Berardinelli-Seip congenital lipodystrophy type 2, as well as several neurological seipinopathies. Despite its importance for human health, the molecular role of seipin is still enigmatic. Seipin is evolutionarily conserved from yeast to humans. In yeast, seipin was recently found to cooperate with the lipid droplet organization (LDO) proteins, Ldo16 and Ldo45, two structurally-related proteins involved in LD function and identity that display remote homology to the human protein promethin/TMEM159. In this study, we show that promethin is indeed an LD-associated protein that forms a complex with seipin, and its localization to the LD surface can be modulated by seipin expression levels. We thus identify promethin as a novel seipin partner protein.
Seipin（BSCL2/SPG17）是脂滴（LD）生物学的关键因素，其功能障碍会导致严重的疾病，包括脂肪储存疾病 Berardinelli-Seip 先天性脂肪营养不良 2 型，以及几种神经 seipinopathies。尽管 seipin 对人类健康很重要，但它的分子作用仍然是个谜。Seipin 在从酵母到人这一进化过程中是保守的。在酵母中，最近发现 seipin 与脂滴组织（LDO）蛋白 Ldo16 和 Ldo45 合作，这两种结构相关的蛋白质参与 LD 功能和特性，与人类蛋白 promethin/TMEM159 具有远程同源性。在这项研究中，我们表明 promethin 确实是一种与脂滴相关的蛋白质，它与 seipin 形成复合物，其在 LD 表面的定位可以通过 seipin 的表达水平来调节。因此，我们将 promethin 鉴定为一种新的 seipin 伴侣蛋白。
