Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization.
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.
Bhattacharya
Moshmi
M
Cell Biology Research Group, The John P. Robarts Research Institute, The University of Western Ontario, 100 Perth Drive, London, Ontario, N6A 5K8, Canada.
Anborgh
Pieter H
PH
Babwah
Andy V
AV
Dale
Lianne B
LB
Dobransky
Tomas
T
Benovic
Jeffery L
JL
Feldman
Ross D
RD
Verdi
Joseph M
JM
Rylett
R Jane
RJ
Ferguson
Stephen S G
SS
D000818:Animals; D019390:Arrestins / Q000737:chemistry / Q000378:metabolism*; D001693:Biological Transport, Active; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D000071557:beta-Arrestins; D020725:ral GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020726:ral Guanine Nucleotide Exchange Factor / Q000737:chemistry / Q000378:metabolism*
D019390:Arrestins; D046911:Macromolecular Substances; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D000071557:beta-Arrestins; D020726:ral Guanine Nucleotide Exchange Factor; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009240:N-Formylmethionine Leucyl-Phenylalanine; D020725:ral GTP-Binding Proteins