A Rab-bit hole: Rab40 GTPases as new regulators of the actin cytoskeleton and cell migration.
A Rab-bit hole: Rab40 GTPases as new regulators of the actin cytoskeleton and cell migration.
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Rab-Bit孔：Rab40 GTPases作为肌动蛋白细胞骨架和细胞迁移的新调节剂。
DOI：
10.3389/fcell.2023.1268922
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞迁移机制的调控对维持机体正常功能至关重要。当迁移失调时，从发育障碍到癌症转移的各种表型都可能发生。参与细胞迁移的主要结构之一是肌动蛋白细胞骨架。肌动蛋白的组装和拆卸形成了各种动态结构，这些结构为细胞适当迁移提供了必要的推力和收缩力。因此，肌动蛋白动力学受到严格调节。传统上，gtpase的Rho家族被认为是细胞迁移过程中肌动蛋白细胞骨架的主要调节因子。总之，这个家族通过刺激特定细胞位置的各种肌动蛋白结构的形成，在迁移细胞中建立极性。然而，虽然Rho gtpase被认为是调节肌动蛋白动力学和细胞迁移的核心机制，但各种其他蛋白质已被确定为肌动蛋白结构和细胞迁移的调节剂。其中一组蛋白质是GTPases的Rab40家族，这是一个进化上和功能上独特的Rabs家族。Rab40起源于双边动物的单一蛋白质，并通过多次复制事件扩展到高等灵长类动物的四蛋白家族。此外，与rabb家族的其他成员不同，Rab40蛋白含有一个位于c末端的细胞因子信号传导抑制因子（SOCS）盒子结构域。通过SOCS盒，Rab40蛋白与Cullin5相互作用形成E3泛素连接酶复合物。作为该复合体的成员，Rab40泛素化其效应物，控制其降解，定位和激活。由于Rab40/Cullin5复合物的底物可以在调节肌动蛋白结构和细胞迁移中发挥作用，Rab40蛋白家族最近成为细胞迁移机制的独特调节剂。
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.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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