beta-Arrestins are important in chemoattractant receptor-induced granule release, a process that may involve Ral-dependent regulation of the actin cytoskeleton. We have identified the Ral GDP dissociation stimulator (Ral-GDS) as a beta-arrestin-binding protein by yeast two-hybrid screening and co-immunoprecipitation from human polymorphonuclear neutrophilic leukocytes (PMNs). Under basal conditions, Ral-GDS is localized to the cytosol and remains inactive in a complex formed with beta-arrestins. In response to formyl-Met-Leu-Phe (fMLP) receptor stimulation, beta-arrestin Ral-GDS protein complexes dissociate and Ral-GDS translocates with beta-arrestin from the cytosol to the plasma membrane, resulting in the Ras-independent activation of the Ral effector pathway required for cytoskeletal rearrangement. The subsequent re-association of beta-arrestin Ral-GDS complexes is associated with the inactivation of Ral signalling. Thus, beta-arrestins regulate multiple steps in the Ral-dependent processes that result in chemoattractant-induced cytoskeletal reorganization.
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Article Synopsis
- - The study investigates how a peptide hormone (PTH) interacts with its receptor (PTHR) and β-arrestin (βarr) to form a ternary complex, which is key for G protein-coupled receptor (GPCR) signaling.
- - Using fluorescent markers and advanced imaging techniques, the research shows that PTHR moves freely in the cell membrane while unbound PTH has limited mobility, indicating a distinct dynamic behavior.
- - The formation of the PTH-PTHR-βarr complex happens in three steps: ligand-receptor collisions, βarr recruitment triggered by a specific lipid (PIP), and final assembly within clathrin clusters, highlighting the importance of PIP in GPCR
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