β-Arrestins regulate a Ral-GDS-Ral effector pathway that mediates cytoskeletal reorganization

• Published in: Nature cell biology Vol. 4; no. 8; pp. 547 - 555
• Main Authors: Ferguson, Stephen S. G, Bhattacharya, Moshmi, Anborgh, Pieter H, Babwah, Andy V, Dale, Lianne B, Dobransky, Tomas, Benovic, Jeffery L, Feldman, Ross D, Verdi, Joseph M, Rylett, R. Jane
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-08-2002
• Subjects: Animals; Arrestins - chemistry; Arrestins - metabolism; beta-Arrestins; Binding proteins; Biological Transport, Active; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Cellular signal transduction; Chemokine receptors; COS Cells; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Humans; Macromolecular Substances; Models, Biological; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - drug effects; Neutrophils - metabolism; Physiological aspects; ral GTP-Binding Proteins - chemistry; ral GTP-Binding Proteins - metabolism; ral Guanine Nucleotide Exchange Factor - chemistry; ral Guanine Nucleotide Exchange Factor - metabolism; Rats; Receptors, Formyl Peptide; Receptors, Immunologic - metabolism; Receptors, Peptide - metabolism; Signal Transduction; Two-Hybrid System Techniques
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb821

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.