Rab family of small GTPases: an updated view on their regulation and functions
Autor: | Yuta Homma, Mitsunori Fukuda, Shu Hiragi |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
organelle post‐translational modification knockout membrane traffic Saccharomyces cerevisiae GTPase Biology Guanosine Diphosphate Biochemistry 03 medical and health sciences 0302 clinical medicine Terminology as Topic Organelle State‐of‐the‐Art Review Animals Guanine Nucleotide Exchange Factors Humans CRISPR GEF Phosphorylation Transport Vesicles Molecular Biology Phylogeny Organelles State‐of‐the‐Art Reviews Effector GTPase-Activating Proteins fungi GAP Biological Transport Cell Biology Phenotype Cell biology effector Eukaryotic Cells 030104 developmental biology rab GTP-Binding Proteins 030220 oncology & carcinogenesis Rab small GTPases Guanosine Triphosphate Guanine nucleotide exchange factor Rab Protein Processing Post-Translational Biogenesis |
Zdroj: | The Febs Journal |
ISSN: | 1742-4658 1742-464X |
DOI: | 10.1111/febs.15453 |
Popis: | 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. The Rab family of small GTPases regulates intracellular membrane trafficking by localizing on specific organelles (or vesicles) and recruiting various effector proteins to facilitate each step of membrane trafficking. In this review article, we provide the most up‐to‐date and comprehensive lists of guanine nucleotide exchange factors, GTPase‐activating proteins, effectors, and knockout phenotypes of mammalian Rabs and discuss recent findings in regard to their regulation and functions. |
Databáze: | OpenAIRE |
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