Mima Joji
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Biophys Rev. 2018 Apr;10(2):543-549. doi: 10.1007/s12551-017-0358-3. Epub 2017 Dec 4.
Membrane tethering is one of the most critical steps to determine the spatiotemporal specificity of membrane trafficking, which is the process to selectively transport proteins, lipids, and other biological molecules to the appropriate locations in eukaryotic cells, such as subcellular organelles, the plasma membrane, and the extracellular space. Based on genetic, cell biological, biochemical, and structural studies, Rab-family small GTPases and a number of Rab-interacting proteins (termed Rab effectors), including coiled-coil tethering proteins and multisubunit tethering complexes, have been proposed to be key protein components for membrane tethering. Nevertheless, indeed whether and how Rab GTPases and their specific Rab effectors directly act upon and catalyze membrane tethering still remains enigmatic. By chemically defined reconstitution of membrane tethering from purified Rab-family GTPase proteins and synthetic liposomal membranes, recent studies have revealed the intrinsic potency of Rab-family GTPases to physically and specifically tether two distinct lipid bilayers of liposomal membranes. Experimental evidence from these reconstitution studies support the novel working model in which Rab-family small GTPases act as a bona fide membrane tether for mediating membrane tethering events in eukaryotic membrane trafficking.
膜拴系是决定膜运输时空特异性的最关键步骤之一，膜运输是将蛋白质、脂质和其他生物分子选择性地运输到真核细胞中适当位置的过程，如亚细胞器、质膜和细胞外空间。基于遗传学、细胞生物学、生物化学和结构研究，Rab家族小GTP酶和许多Rab相互作用蛋白（称为Rab效应器），包括卷曲螺旋拴系蛋白和多亚基拴系复合物，被认为是膜拴系的关键蛋白质成分。然而，Rab GTP酶及其特定的Rab效应器是否以及如何直接作用并催化膜拴系实际上仍然是个谜。通过从纯化的Rab家族GTP酶蛋白和合成脂质体膜进行化学定义的膜拴系重建，最近的研究揭示了Rab家族GTP酶在物理上特异性拴系脂质体膜的两个不同脂质双层的内在能力。这些重建研究的实验证据支持了一种新的工作模型，即Rab家族小GTP酶作为真正的膜拴系物，在真核细胞膜运输中介导膜拴系事件。
