Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan; Biosignal Research Center, Kobe University, Kobe, Hyogo, Japan; and Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
Physiol Rev. 2014 Oct;94(4):1219-48. doi: 10.1152/physrev.00040.2013.
All cellular compartments are separated from the external environment by a membrane, which consists of a lipid bilayer. Subcellular structures, including clathrin-coated pits, caveolae, filopodia, lamellipodia, podosomes, and other intracellular membrane systems, are molded into their specific submicron-scale shapes through various mechanisms. Cells construct their micro-structures on plasma membrane and execute vital functions for life, such as cell migration, cell division, endocytosis, exocytosis, and cytoskeletal regulation. The plasma membrane, rich in anionic phospholipids, utilizes the electrostatic nature of the lipids, specifically the phosphoinositides, to form interactions with cytosolic proteins. These cytosolic proteins have three modes of interaction: 1) electrostatic interaction through unstructured polycationic regions, 2) through structured phosphoinositide-specific binding domains, and 3) through structured domains that bind the membrane without specificity for particular phospholipid. Among the structured domains, there are several that have membrane-deforming activity, which is essential for the formation of concave or convex membrane curvature. These domains include the amphipathic helix, which deforms the membrane by hemi-insertion of the helix with both hydrophobic and electrostatic interactions, and/or the BAR domain superfamily, known to use their positively charged, curved structural surface to deform membranes. Below the membrane, actin filaments support the micro-structures through interactions with several BAR proteins as well as other scaffold proteins, resulting in outward and inward membrane micro-structure formation. Here, we describe the characteristics of phospholipids, and the mechanisms utilized by phosphoinositides to regulate cellular events. We then summarize the precise mechanisms underlying the construction of membrane micro-structures and their involvements in physiological and pathological processes.
所有细胞区室都通过细胞膜与外部环境隔开，细胞膜由脂质双层组成。亚细胞结构，包括网格蛋白包被的凹陷、小窝、丝状伪足、片状伪足、足突和其他细胞内膜系统，通过各种机制被塑造成特定的亚微米尺度形状。细胞在质膜上构建其微结构，并执行生命的重要功能，如细胞迁移、细胞分裂、内吞作用、胞吐作用和细胞骨架调节。富含阴离子磷脂的质膜利用脂质的静电性质，特别是磷酸肌醇，与胞质蛋白形成相互作用。这些胞质蛋白有三种相互作用模式：1）通过无结构的多阳离子区域的静电相互作用，2）通过结构的磷酸肌醇特异性结合域，和 3）通过结合膜而没有对特定磷脂特异性的结构域。在结构域中，有几个具有膜变形活性，这对于凹面或凸面膜曲率的形成是必不可少的。这些结构域包括通过疏水和亲电相互作用使螺旋半插入来变形膜的两亲性螺旋，和/或已知使用其带正电荷的弯曲结构表面来变形膜的 BAR 结构域超家族。在膜下，肌动蛋白丝通过与几个 BAR 蛋白以及其他支架蛋白的相互作用来支撑微结构，导致向外和向内的膜微结构形成。在这里，我们描述了磷脂的特性，以及磷酸肌醇用于调节细胞事件的机制。然后，我们总结了构建膜微结构的精确机制及其在生理和病理过程中的参与。
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