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.

膜流动性对生命至关重要，并且在狭窄的状态下受到严格控制。复杂的生物膜的流动性在很大程度上取决于掺入膜脂质中的饱和和不饱和脂肪酸的比例。即使对脂肪酸去饱和的机制进行了深入研究，但膜流动性的分子传感器却尚不清楚。使用和定量的，基于质谱的脂肪分析酿酒酵母，我们将筛选在体内影响脂质饱和度的基因，并通过在定义的膜环境中纯化和重新建立来研究其体外效应的机制。我最近将内质网（ER）质量控制机制的一个组成部分确定为膜流动性的推定传感器，并可以证明其结合不饱和脂肪酸的能力。这些发现导致了我的假设：负责ER源蛋白的机器的底物光谱直接由脂肪酸调节，并且这些机制负责膜的流动性稳态。为了检验这一假设，我开发了针对脂质饱和度微调细胞脂质体的方法，并将量化这些垂直蛋白的蛋白质更换和分泌的效果。该建议旨在更好地理解膜脂质和蛋白质稳态以及基本分子机制的分子机制。

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）

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