Abstract
Ras analog in brain (Rab) proteins are small guanosine triphosphatases (GTPases) that belong to the Ras-like GTPase superfamily, and they can regulate vesicle trafficking. Rab proteins alternate between an activated (GTP-bound) state and an inactivated (GDP-bound) state. Early endosome marker Rab5 GTPase, a key member of the Rab family, plays a crucial role in endocytosis and membrane transport. The activated-state Rab5 recruits its effectors and regulates the internalization and trafficking of membrane receptors by regulating vesicle fusion and receptor sorting in the early endosomes. In this review, we summarize the role of small Rab GTPases Rab5 in membrane receptor trafficking and the activation of signaling pathways, such as Ras/MAPK and PI3K/Akt, which ultimately affect cell growth, apoptosis, tumorigenesis, and tumor development. This review may provide some insights for our future research and novel therapeutic targets for diseases.
Highlights
Ras analog in brain (Rab) proteins, belonging to the largest family of Ras superfamily, are small guanosine diphosphate (GTP)- bound proteins that regulate intracellular trafficking pathways [1]. ere are more than 60 distinct proteins in humans, which constitute 41 functional subfamilies with tissue specificity
Rab proteins are present in monomeric forms, and the amino acid sequence similarity of Rab family members ranges from 35% to 80% [2]
Rab guanosine triphosphatases (GTPases) can transform between the GTP-bound activated form and guanosine diphosphate (GDP)-bound inactivated form [8]. e GTP-Rab is located on the plasma membrane, and GDPRab is located in the cytoplasm. e transformation between the activated and inactivated forms requires three crucial regulators: GDP dissociation inhibitor (GDI), guanine nucleotide exchange factor (GEF), and GTPase activating protein (GAP)
Summary
Ras analog in brain (Rab) proteins, belonging to the largest family of Ras superfamily, are small guanosine diphosphate (GTP)- bound proteins that regulate intracellular trafficking pathways [1]. ere are more than 60 distinct proteins in humans, which constitute 41 functional subfamilies with tissue specificity. Activated Rab interacts with its effectors and involves in vesicular transport, membrane trafficking, and signaling pathways [4]. Further studies showed that the mutants of both SEC4 and YPT1 could encode small GTP-bound proteins, and the structural and functional analogues of SEC and YPT were cloned from a rat brain library and named Rab [7]. Rab proteins share similar structures, generally containing two cysteine residues at the carboxyl terminus generally, which appear in the form of -CC, -CXC, -CCXX, -CXXX, or -CCXXX (X represents any amino acid) and act as the membrane localization signal [8]. Rab GTPases can transform between the GTP-bound activated form and GDP-bound inactivated form [8]. Rab family proteins perform different functions in membrane receptor trafficking and signaling pathways because they bind to different effectors [4]. Rab GTPases play their roles in organelles connection at different stages of vesicular transport, including budding, transport, tethering, docking, and fusion stages [11]
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