Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation.

Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation.
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DOI:
10.1083/jcb.201704122
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发表时间:
2018-01-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Bohnert M
Bohnert M
中科院分区:
其他
文献类型:
--
作者:
Eisenberg-Bord M;Mari M;Weill U;Rosenfeld-Gur E;Moldavski O;Castro IG;Soni KG;Harpaz N;Levine TP;Futerman AH;Reggiori F;Bankaitis VA;Schuldiner M;Bohnert M

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Eisenberg-Bord等人描述了一种具有独特蛋白质组的脂滴(LD)亚群,该蛋白质组邻近核-液泡连接接触位点。他们确定了LD机制,它与脂肪代谢障碍因子seipin合作,作为LD身份的关键决定因素,并提出了功能性细胞器多样化的机制。已经观察到单个细胞的脂滴(LD)池内的功能异质性,但潜在的机制仍然是谜。在这里,我们报告一个专门的LD亚群的特点是一个独特的蛋白质组和一个明确的地理位置在核-空泡交界处接触网站的识别。在寻找决定这些LD身份的因素时,我们筛选了106,000个酵母突变体,以寻找亚群标记Pdr 16的靶向丢失,并将Ldo 45(45 kD的LD组织蛋白)鉴定为关键的靶向决定因素。Ldo 45是连接两个相邻基因(YMR 147 W和YMR 148 W/OSW 5/LDO 16)的剪接事件的产物。我们发现,LDO蛋白与LD生物合成组分seipin合作,并通过定义定位和表面蛋白组成建立LD身份。我们的研究提出了一种建立细胞器功能分化的机制,为更好地理解细胞中的代谢决定打开了大门。
Eisenberg-Bord et al. describe a lipid droplet (LD) subpopulation with a unique proteome, which is adjacent to the nucleus–vacuole junction contact site. They identify the LD machinery, which cooperates with the lipodystrophy factor seipin as a key determinant of LD identity and suggest a mechanism for functional organelle diversification. Functional heterogeneity within the lipid droplet (LD) pool of a single cell has been observed, yet the underlying mechanisms remain enigmatic. Here, we report on identification of a specialized LD subpopulation characterized by a unique proteome and a defined geographical location at the nucleus–vacuole junction contact site. In search for factors determining identity of these LDs, we screened ∼6,000 yeast mutants for loss of targeting of the subpopulation marker Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial targeting determinant. Ldo45 is the product of a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins cooperate with the LD biogenesis component seipin and establish LD identity by defining positioning and surface-protein composition. Our studies suggest a mechanism to establish functional differentiation of organelles, opening the door to better understanding of metabolic decisions in cells.
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