A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress.
A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress.
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DOI：
10.1016/j.molcel.2013.06.014
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发表时间：
2013-08-22
期刊：
影响因子：
16
通讯作者：
Ernst, Robert
中科院分区：
文献类型：
--
作者：
Surma, Michal A.;Klose, Christian;Peng, Debby;Shales, Michael;Mrejen, Caroline;Stefanko, Adam;Braberg, Hannes;Gordon, David E.;Vorkel, Daniela;Ejsing, Christer S.;Farese, Robert, Jr.;Simons, Kai;Krogan, Nevan J.;Ernst, Robert
生物膜很复杂，其体内平衡的机制尚不完全清楚。在这里，我们提出了一个定量遗传相互作用图（E-MAP）集中在脂质生物学的各个方面，包括脂质代谢，分选和贩运。该E-MAP包含约250，000个阴性和阳性遗传相互作用评分，并鉴定了蛋白质质量控制途径与脂质双层稳态的分子串扰。Ubx 2 p是内质网相关降解途径的一个组成部分，是必需脂肪酸（FA）去饱和酶Ole 1 p的关键上游调节因子。Ubx 2 p的丢失影响OLE 1的转录控制，导致FA去饱和受损和向更饱和的膜脂质的严重转变。在缺乏UBX 2的细胞中观察到的未折叠蛋白反应和异常核膜形态的诱导都被不饱和脂肪酸的补充抑制。我们的研究结果指向膜稳态的专用双层应力反应的存在。
Biological membranes are complex, and the mechanisms underlying their homeostasis are incompletely understood. Here, we present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains ~250,000 negative and positive genetic interaction scores and identifies a molecular crosstalk of protein quality control pathways with lipid bilayer homeostasis. Ubx2p, a component of the endoplasmic-reticulum-associated degradation pathway, surfaces as a key upstream regulator of the essential fatty acid (FA) desaturase Ole1p. Loss of Ubx2p affects the transcriptional control of OLE1, resulting in impaired FA desaturation and a severe shift toward more saturated membrane lipids. Both the induction of the unfolded protein response and aberrant nuclear membrane morphologies observed in cells lacking UBX2 are suppressed by the supplementation of unsaturated FAs. Our results point toward the existence of dedicated bilayer stress responses for membrane homeostasis.
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