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Rab family of small GTPases: an updated view on their regulation and functions.
The FEBS Journal ( IF 5.4 ) Pub Date : 2020-06-15 , DOI: 10.1111/febs.15453
Yuta Homma 1 , Shu Hiragi 1 , Mitsunori Fukuda 1
Affiliation  

The Rab family of small GTPases regulates intracellular membrane trafficking by orchestrating the biogenesis, transport, tethering, and fusion of membrane‐bound organelles and vesicles. Like other small GTPases, Rabs cycle between two states, an active (GTP‐loaded) state and an inactive (GDP‐loaded) state, and their cycling is catalyzed by guanine nucleotide exchange factors (GEFs) and GTPase‐activating proteins (GAPs). Because an active form of each Rab localizes on a specific organelle (or vesicle) and recruits various effector proteins to facilitate each step of membrane trafficking, knowing when and where Rabs are activated and what effectors Rabs recruit is crucial to understand their functions. Since the discovery of Rabs, they have been regarded as one of the central hubs for membrane trafficking, and numerous biochemical and genetic studies have revealed the mechanisms of Rab functions in recent years. The results of these studies have included the identification and characterization of novel GEFs, GAPs, and effectors, as well as post‐translational modifications, for example, phosphorylation, of Rabs. Rab functions beyond the simple effector‐recruiting model are also emerging. Furthermore, the recently developed CRISPR/Cas technology has enabled acceleration of knockout analyses in both animals and cultured cells and revealed previously unknown physiological roles of many Rabs. In this review article, we provide the most up‐to‐date and comprehensive lists of GEFs, GAPs, effectors, and knockout phenotypes of mammalian Rabs and discuss recent findings in regard to their regulation and functions.

中文翻译:

小型GTPases Rab系列:有关其法规和功能的最新观点。

小型GTPases的Rab家族通过协调膜结合细胞器和囊泡的生物发生,运输,栓系和融合来调节细胞内膜运输。像其他小型GTPases一样,Rabs在两个状态(活动(装载GTP的)状态和非活动(GDP装载的)状态)之间循环,它们的循环受鸟嘌呤核苷酸交换因子(GEF)和GTPase激活蛋白(GAP)催化。 。由于每个Rab的活性形式都位于特定的细胞器(或囊泡)上,并且募集各种效应蛋白来促进膜运输的每个步骤,因此了解何时以及在何处激活Rab以及募集哪种效应子对于理解其功能至关重要。自发现Rabs以来,它们就被视为膜运输的中心枢纽之一,近年来,许多生化和遗传研究揭示了Rab功能的机制。这些研究的结果包括新型GEF,GAP和效应子的鉴定和表征,以及Rabs的翻译后修饰,例如磷酸化。Rab的功能已经超越了简单的效应子招募模型。此外,最近开发的CRISPR / Cas技术可以加速动物和培养细胞的基因敲除分析,并揭示了许多Rab以前未知的生理作用。在这篇综述文章中,我们提供了哺乳动物Rabs的GEF,GAP,效应子和敲除表型的最新,最全面的列表,并讨论了有关其调控和功能的最新发现。
更新日期:2020-06-15
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