Membrane bending by protein phase separation
Membrane bending by protein phase separation
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DOI：
10.1101/2020.05.21.109751
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发表时间：
2020-05
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影响因子：
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通讯作者：
Feng Yuan;H. Alimohamadi;Brandon Bakka;Andrea N. Trementozzi;K. Day;N. Fawzi;P. Rangamani;J. Stacho
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文献类型：
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作者：
Feng Yuan;H. Alimohamadi;Brandon Bakka;Andrea N. Trementozzi;K. Day;N. Fawzi;P. Rangamani;J. Stacho
意义细胞膜呈现出一套精致的高度弯曲和弯曲的形状，这对从内吞到细胞分裂的各种细胞功能是必不可少的。流行的观点认为，膜弯曲是由具有弯曲形状的蛋白质驱动的，这些蛋白质在膜表面聚集形成固体支架。相反，我们在这里展示了在膜上形成液状组装的蛋白质也是弯曲的有力驱动因素。这些“液体支架”将压应力施加到膜表面，生成了一系列多样和动态的膜形状。这些数据是在整个细胞中识别出类似液体的蛋白质组件的时候出现的，这表明蛋白质液体可能在塑造细胞膜方面发挥着重要作用。膜弯曲是一种普遍存在的细胞过程，是膜运输、细胞运动、细胞器生物发生和细胞分裂所必需的。使用特定结构特征与膜结合的蛋白质，如楔形两亲性螺旋和新月形支架，被认为是膜弯曲的主要驱动因素。然而，许多膜结合蛋白都有大量的内在无序区域，缺乏稳定的三维结构。有趣的是，最近发现许多这些无序结构域形成了由弱的多价接触稳定的网络，导致蛋白质液体相在膜表面组装。在这里，我们问膜相关蛋白液体如何影响膜曲率。我们发现，合成的和细胞来源的膜泡表面的蛋白质相分离在膜平面上产生了相当大的压应力。这种压力驱使膜向内弯曲，产生蛋白质内衬的膜小管。这一过程的一个简单的力学模型准确地预测了膜的刚性与膜管直径之间的实验测量关系。这一机制的发现可能与广泛的细胞突起有关，表明膜重塑不仅仅是结构化支架所特有的，还可以由迅速出现的聚集在膜上的类液体蛋白质网络驱动。
Significance Cellular membranes take on an elaborate set of highly curved and bent shapes which are essential to diverse cellular functions from endocytosis to cell division. The prevailing view has been that membrane bending is driven by proteins with curved shapes, which assemble at the membrane surface to form solid scaffolds. In contrast, here we show that proteins which form liquid-like assemblies on membranes are also potent drivers of bending. These “liquid scaffolds” apply compressive stress to the membrane surface, generating a diverse and dynamic family of membrane shapes. These data, which come at a time when liquid-like protein assemblies are being identified throughout the cell, suggest that protein liquids may play an important role in shaping cellular membranes. Membrane bending is a ubiquitous cellular process that is required for membrane traffic, cell motility, organelle biogenesis, and cell division. Proteins that bind to membranes using specific structural features, such as wedge-like amphipathic helices and crescent-shaped scaffolds, are thought to be the primary drivers of membrane bending. However, many membrane-binding proteins have substantial regions of intrinsic disorder which lack a stable three-dimensional structure. Interestingly, many of these disordered domains have recently been found to form networks stabilized by weak, multivalent contacts, leading to assembly of protein liquid phases on membrane surfaces. Here we ask how membrane-associated protein liquids impact membrane curvature. We find that protein phase separation on the surfaces of synthetic and cell-derived membrane vesicles creates a substantial compressive stress in the plane of the membrane. This stress drives the membrane to bend inward, creating protein-lined membrane tubules. A simple mechanical model of this process accurately predicts the experimentally measured relationship between the rigidity of the membrane and the diameter of the membrane tubules. Discovery of this mechanism, which may be relevant to a broad range of cellular protrusions, illustrates that membrane remodeling is not exclusive to structured scaffolds but can also be driven by the rapidly emerging class of liquid-like protein networks that assemble at membranes.