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首页> 外文期刊>The EMBO journal. >Seipin regulates ER-lipid droplet contacts and cargo delivery
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Seipin regulates ER-lipid droplet contacts and cargo delivery

机译：Seipin调节ER-lipid液滴接触货物交付

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摘要

Seipin is an endoplasmic reticulum (ER) membrane protein implicated in lipid droplet (LD) biogenesis and mutated in severe congenital lipodystrophy (BSCL2). Here, we show that seipin is stably associated with nascent ER-LD contacts in human cells, typically via one mobile focal point per LD. Seipin appears critical for such contacts since ER-LD contacts were completely missing or morphologically aberrant in seipin knockout and BSCL2 patient cells. In parallel, LD mobility was increased and protein delivery from the ER to LDs to promote LD growth was decreased. Moreover, while growing LDs normally acquire lipid and protein constituents from the ER, this process was compromised in seipin-deficient cells. In the absence of seipin, the initial synthesis of neutral lipids from exogenous fatty acid was normal, but fatty acid incorporation into neutral lipids in cells with pre-existing LDs was impaired. Together, our data suggest that seipin helps to connect newly formed LDs to the ER and that by stabilizing ER-LD contacts seipin facilitates the incorporation of protein and lipid cargo into growing LDs in human cells.
机译：Seipin是内质网(ER)膜蛋白质与脂滴(LD)生物起源和严重的先天性变异脂肪代谢障碍(BSCL2)。稳定与新生ER-LD相关联系人在人类细胞中,通常通过一个移动焦点点/ LD。Seipin出现这样的关键自ER-LD接触完全接触缺失或seipin形态学异常基因敲除和BSCL2病人细胞。流动性增加,蛋白质从交付ER摩门教的促进LD增长下降。此外,虽然像通常获得增长脂质和蛋白质组分的呃,这个过程是seipin-deficient妥协细胞。从外源性脂肪酸合成中性脂质酸是正常的,但脂肪酸结合与已有的中性脂质细胞中摩门教是受损的。seipin有助于新成立的摩门教的连接呃,通过稳定seipin ER-LD接触促进蛋白质和结合在人类细胞中脂质货物到摩门教增长。

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