Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Mol Cell Biol. 2023 Jan;24(1):63-78. doi: 10.1038/s41580-022-00511-9. Epub 2022 Aug 2.
Curved membranes are key features of intracellular organelles, and their generation involves dynamic protein complexes. Here we describe the fundamental mechanisms such as the hydrophobic insertion, scaffolding and crowding mechanisms these proteins use to produce membrane curvatures and complex shapes required to form intracellular organelles and vesicular structures involved in endocytosis and secretion. For each mechanism, we discuss its cellular functions as well as the underlying physical principles and the specific membrane properties required for the mechanism to be feasible. We propose that the integration of individual mechanisms into a highly controlled, robust process of curvature generation often relies on the assembly of proteins into coats. How cells unify and organize the curvature-generating factors at the nanoscale is presented for three ubiquitous coats central for membrane trafficking in eukaryotes: clathrin-coated pits, caveolae, and COPI and COPII coats. The emerging theme is that these coats arrange and coordinate curvature-generating factors in time and space to dynamically shape membranes to accomplish membrane trafficking within cells.
弯曲的膜是细胞内细胞器的关键特征,其生成涉及动态蛋白质复合物。在这里,我们描述了这些蛋白质用于产生膜曲率和复杂形状的基本机制,这些形状是形成细胞内细胞器和参与胞吞作用和分泌的囊泡结构所必需的。对于每种机制,我们讨论了其细胞功能以及潜在的物理原理和机制可行所需的特定膜特性。我们提出,将单个机制整合到高度受控、稳健的曲率生成过程中,通常依赖于蛋白质组装成外壳。我们介绍了在真核生物中三种常见的膜运输核心蛋白:网格蛋白包被小凹、窖蛋白和 COPI 和 COPII 包被,细胞如何在纳米尺度上将曲率生成因子统一和组织起来。一个新兴的主题是,这些外壳在时间和空间上排列和协调曲率生成因子,以动态地塑造膜,从而在细胞内完成膜运输。