Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization

Moshmi Bhattacharya; Pieter H Anborgh; Andy V Babwah; Lianne B Dale; Tomas Dobransky; Jeffery L Benovic; Ross D Feldman; Joseph M Verdi; R Jane Rylett; Stephen S G Ferguson

doi:10.1038/ncb821

Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization

Nat Cell Biol. 2002 Aug;4(8):547-55. doi: 10.1038/ncb821.

Authors

Moshmi Bhattacharya¹, Pieter H Anborgh, Andy V Babwah, Lianne B Dale, Tomas Dobransky, Jeffery L Benovic, Ross D Feldman, Joseph M Verdi, R Jane Rylett, Stephen S G Ferguson

Affiliation

¹ Cell Biology Research Group, The John P. Robarts Research Institute, The University of Western Ontario, 100 Perth Drive, London, Ontario, N6A 5K8, Canada.

PMID: 12105416
DOI: 10.1038/ncb821

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arrestins / chemistry
Arrestins / metabolism*
Biological Transport, Active
COS Cells
Cell Line
Cell Membrane / drug effects
Cell Membrane / metabolism
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
Rats
Receptors, Formyl Peptide
Receptors, Immunologic / metabolism
Receptors, Peptide / metabolism
Signal Transduction
Two-Hybrid System Techniques
beta-Arrestins
ral GTP-Binding Proteins / chemistry
ral GTP-Binding Proteins / metabolism*
ral Guanine Nucleotide Exchange Factor / chemistry
ral Guanine Nucleotide Exchange Factor / metabolism*

Substances

Arrestins
Macromolecular Substances
Receptors, Formyl Peptide
Receptors, Immunologic
Receptors, Peptide
beta-Arrestins
ral Guanine Nucleotide Exchange Factor
Guanosine 5'-O-(3-Thiotriphosphate)
N-Formylmethionine Leucyl-Phenylalanine
ral GTP-Binding Proteins