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Published on: December 29, 2017
Ral: mediator of membrane trafficking
Ellen M van Dam1, Phillip J Robinson
1Cell Signalling Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.
Abstract:
Ral is a multifunctional small GTPase involved in tumorigenesis and in controlling intracellular membrane trafficking. It is mainly activated by factors downstream of Ras, or independently of these factors and operates by protein-protein interactions with an expanding repertoire of partners. RalA is a positive regulator of calcium-evoked exocytosis via binding phospholipase D and is involved in G protein coupled receptor signalling by binding phospholipase C-delta1. The binding of Ral to calmodulin links to intracellular trafficking events. Another link is direct binding of activated Ral (Ral-GTP) to the endocytic and exocytic machineries. Ral-GTP binds RalBP1, which connects to receptor-mediated endocytosis via AP-2. Alternatively, Ral-GTP binds the exocyst complex, which controls secretory vesicle trafficking in regulated secretion and filopodia formation. Thus, Ral-GTP "chooses" between different membrane trafficking pathways. Other Ral partners are still being uncovered that may provide further mechanistic insights into how Ral controls diverse membrane trafficking pathways.
Insights
Ral GTPase regulates cell processes like tumorigenesis and membrane trafficking. It interacts with partners to control exocytosis, signaling, and vesicle movement, impacting diverse cellular pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Ral GTPase is a key regulator of tumorigenesis and intracellular membrane trafficking.
- It functions through protein-protein interactions with diverse partners.
- RalA specifically influences calcium-evoked exocytosis and G protein-coupled receptor signaling.
Purpose of the Study:
- To elucidate the multifaceted roles of Ral GTPase in cellular processes.
- To detail the interaction partners and mechanisms by which Ral controls membrane trafficking pathways.
- To highlight Ral's involvement in endocytosis, exocytosis, and signaling.
Main Methods:
- Literature review and synthesis of existing research on Ral GTPase.
- Analysis of protein-protein interactions involving Ral and its partners (e.g., phospholipase D, phospholipase C-delta1, calmodulin, RalBP1, exocyst complex).
- Examination of Ral's role in specific cellular events like exocytosis, endocytosis, and filopodia formation.
Main Results:
- Ral GTPase, particularly RalA, acts as a multifunctional regulator.
- It binds to various partners, including phospholipase D, phospholipase C-delta1, calmodulin, RalBP1, and the exocyst complex.
- Activated Ral (Ral-GTP) directly engages with endocytic and exocytic machinery, influencing receptor-mediated endocytosis and secretory vesicle trafficking.
Conclusions:
- Ral GTPase plays a critical role in directing distinct membrane trafficking pathways.
- Its interactions with diverse partners provide mechanistic insights into its control over cellular functions.
- Further research into novel Ral partners will deepen our understanding of its regulatory roles.
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