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Molekulare Mechanismen des Zwiegesprächs von Proteinumsatz und Membranfluidität

蛋白质周转与膜流动性相互作用的分子机制

基本信息

批准号：
213357820
负责人：
Professor Dr. Robert Ernst
金额：
--
依托单位：
Fachrichtung Medizinische Biochemie und Molekularbiologie
依托单位国家：
德国
项目类别：
Independent Junior Research Groups
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/213357820?language=en
关键词：
Molekulare Mechanismen des Zwiegespr chs

项目摘要

Membrane fluidity is essential for life and tightly controlled within a narrow regime. The fluidity of a complex biological membrane is largely dependent on the fraction of saturated and unsaturated fatty acids incorporated into membrane lipids. Even though the mechanisms of fatty acid desaturation have been intensively studied, the molecular sensors of membrane fluidity are not known. Using and quantitative, mass-spectrometry based lipidomics of Saccharomyces cerevisiae, we will screen for genes that affect lipid saturation in vivo and study the mechanism behind their effects in vitro by purification and reconstitution in defined membrane environments. I have recently identified a component of the endoplasmic reticulum (ER) quality control machinery as a putative sensor of membrane fluidity and could demonstrate its capacity to bind unsaturated fatty acids. These findings lead to my hypothesis that the substrate spectrum of the machineries responsible for turnover of ER-derived proteins is directly modulated by fatty acids, and that these mechanisms are responsible for membrane fluidity homeostasis. To test this hypothesis, I have developed methods to fine-tune the cellular lipidome with respect to lipid saturation and will quantify the effects of these pertubations protein turnover and secretion. This proposal aims at a better understanding of the molecular mechanism underlying membrane lipid and protein homeostasis and the underlying molecular mechanisms.

膜的流动性对于生命至关重要，并且在狭窄的范围内受到严格控制。复杂生物膜的流动性很大程度上取决于膜脂中饱和和不饱和脂肪酸的比例。尽管脂肪酸去饱和的机制已被深入研究，但膜流动性的分子传感器尚不清楚。使用基于定量、质谱分析的酿酒酵母脂质组学，我们将筛选影响体内脂质饱和度的基因，并通过在特定的膜环境中纯化和重构来研究其体外影响背后的机制。我最近发现内质网（ER）质量控制机制的一个组成部分是膜流动性的假定传感器，并且可以证明其结合不饱和脂肪酸的能力。这些发现引出了我的假设，即负责内质网衍生蛋白质周转的机制的底物谱直接受脂肪酸调节，并且这些机制负责膜流动性稳态。为了检验这一假设，我开发了一些方法来微调细胞脂质组的脂质饱和度，并将量化这些扰动蛋白质周转和分泌的影响。该提案旨在更好地理解膜脂和蛋白质稳态的分子机制以及潜在的分子机制。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Homeostatic control of biological membranes by dedicated lipid and membrane packing sensors

通过专用脂质和膜填充传感器对生物膜进行稳态控制

DOI：
10.1515/hsz-2015-0130
发表时间：
2015
期刊：
Biological Chemistry
影响因子：
3.7
作者：
Hofbauer;Saénz
通讯作者：
Saénz

A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress.

DOI：
10.1016/j.molcel.2013.06.014
发表时间：
2013-08-22
期刊：
MOLECULAR CELL
影响因子：
16
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
通讯作者：
Ernst, Robert

Crosstalk of lipid and protein homeostasis to maintain membrane function

脂质和蛋白质稳态的串扰以维持膜功能