细胞迁移机制的调控对于维持正常生物体功能至关重要。当迁移失调时，会导致从发育障碍到癌症转移等多种表型。细胞迁移中的一个主要结构是肌动蛋白细胞骨架。肌动蛋白的聚合和解聚形成各种动态结构，为细胞适当迁移提供推动和收缩力。因此，肌动蛋白动力学受到严格调控。经典上，Rho家族GTP酶被认为是细胞迁移过程中肌动蛋白细胞骨架的主要调控因子。该家族通过刺激特定细胞区域内的各种肌动蛋白结构的形成，为迁移细胞建立极性。然而，尽管Rho GTP酶被认为是调控肌动蛋白动力学和细胞迁移的核心机制，但已经确认了一系列其它蛋白质作为肌动蛋白结构和细胞迁移的调节因子。其中之一是Rab40家族GTP酶，一个具有进化和功能上独特的Rab家族。Rab40起源于双侧动物类中的单个蛋白质，经过多次复制事件，在较高等灵长类动物中扩展成为一个由四个蛋白质组成的家族。此外，与Rab家族的其它成员不同，Rab40蛋白质在C-末端具有抑制细胞因子信号(SOCS)盒结构域。通过SOCS盒，Rab40蛋白质与Cullin5相互作用形成E3泛素连接酶复合物。作为该复合物的成员，Rab40蛋白质通过泛素化调控其效应蛋白的降解、定位和活化。由于Rab40/Cullin5复合物的底物能够参与调控肌动蛋白结构和细胞迁移，Rab40蛋白质家族最近被认为是细胞迁移机制的独特调节因子。© 2023 Neumann and Prekeris。

The regulation of machinery involved in cell migration is vital to the maintenance of proper organism function. When migration is dysregulated, a variety of phenotypes ranging from developmental disorders to cancer metastasis can occur. One of the primary structures involved in cell migration is the actin cytoskeleton. Actin assembly and disassembly form a variety of dynamic structures which provide the pushing and contractile forces necessary for cells to properly migrate. As such, actin dynamics are tightly regulated. Classically, the Rho family of GTPases are considered the major regulators of the actin cytoskeleton during cell migration. Together, this family establishes polarity in the migrating cell by stimulating the formation of various actin structures in specific cellular locations. However, while the Rho GTPases are acknowledged as the core machinery regulating actin dynamics and cell migration, a variety of other proteins have become established as modulators of actin structures and cell migration. One such group of proteins is the Rab40 family of GTPases, an evolutionarily and functionally unique family of Rabs. Rab40 originated as a single protein in the bilaterians and, through multiple duplication events, expanded to a four-protein family in higher primates. Furthermore, unlike other members of the Rab family, Rab40 proteins contain a C-terminally located suppressor of cytokine signaling (SOCS) box domain. Through the SOCS box, Rab40 proteins interact with Cullin5 to form an E3 ubiquitin ligase complex. As a member of this complex, Rab40 ubiquitinates its effectors, controlling their degradation, localization, and activation. Because substrates of the Rab40/Cullin5 complex can play a role in regulating actin structures and cell migration, the Rab40 family of proteins has recently emerged as unique modulators of cell migration machinery.Copyright © 2023 Neumann and Prekeris.