Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging.
Cholesterol Regulation of Membrane Proteins Revealed by Two-Color Super-Resolution Imaging.
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双色超分辨率成像揭示膜蛋白的胆固醇调节。
DOI：
10.3390/membranes13020250
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发表时间：
2023-02-20
期刊：
影响因子：
4.2
通讯作者：
中科院分区：
文献类型：
--
作者：
胆固醇和磷脂酰肌醇 4,5-二磷酸 (PIP2) 是调节所有细胞质膜中蛋白质功能的疏水性分子。在这篇综述中，我们讨论了胆固醇浓度的变化如何引起膜蛋白的纳米级（<200 nm）运动以调节其功能。众所周知，胆固醇会将许多膜蛋白（通常是棕榈酰化蛋白）与长链饱和脂质聚集在一起。尽管 PIP2 以门控离子通道而闻名，但在本篇综述中，我们将讨论第二个独立功能，即作为纳米级蛋白质运动调节剂，对抗胆固醇聚集。对蛋白质在纳米级脂质域之间运动的理解主要是通过最近超分辨率成像的出现以及双色技术的建立来标记与蛋白质分开的脂质。我们讨论了成像标记技术、它们的优点和缺点，以及如何使用它们来揭示离子通道、转运蛋白和酶功能的新机制。在这些机制中，我们描述了底物和配体的呈递以及它们快速有效地激活酶、门通道和转运蛋白的能力。最后，我们定义了胆固醇调节蛋白 (CRP)，并讨论了通过超分辨率成像观察到的 PIP2 在对抗胆固醇调节中的作用。
Cholesterol and phosphatidyl inositol 4,5-bisphosphate (PIP2) are hydrophobic molecules that regulate protein function in the plasma membrane of all cells. In this review, we discuss how changes in cholesterol concentration cause nanoscopic (<200 nm) movements of membrane proteins to regulate their function. Cholesterol is known to cluster many membrane proteins (often palmitoylated proteins) with long-chain saturated lipids. Although PIP2 is better known for gating ion channels, in this review, we will discuss a second independent function as a regulator of nanoscopic protein movement that opposes cholesterol clustering. The understanding of the movement of proteins between nanoscopic lipid domains emerged largely through the recent advent of super-resolution imaging and the establishment of two-color techniques to label lipids separate from proteins. We discuss the labeling techniques for imaging, their strengths and weakness, and how they are used to reveal novel mechanisms for an ion channel, transporter, and enzyme function. Among the mechanisms, we describe substrate and ligand presentation and their ability to activate enzymes, gate channels, and transporters rapidly and potently. Finally, we define cholesterol-regulated proteins (CRP) and discuss the role of PIP2 in opposing the regulation of cholesterol, as seen through super-resolution imaging.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1083/jcb.200207113
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ehehalt R;Keller P;Haass C;Thiele C;Simons K
通讯作者：
Simons K
影响因子：
15.9
作者：
DeSpenza T Jr;Carlson M;Panchagnula S;Robert S;Duy PQ;Mermin-Bunnell N;Reeves BC;Kundishora A;Elsamadicy AA;Smith H;Ocken J;Alper SL;Jin SC;Hoffman EJ;Kahle KT
通讯作者：
Kahle KT
影响因子：
16.6
作者：
Deng, Zengqin;Maksaev, Grigory;Yuan, Peng
通讯作者：
Yuan, Peng
DOI：
10.1073/pnas.1407160111
发表时间：
2014-09-16
影响因子：
11.1
作者：
Comoglio, Yannick;Levitz, Joshua;Sandoz, Guillaume
通讯作者：
Sandoz, Guillaume