title: The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration.
abstract: The Gβγ subunits of heterotrimeric G proteins transmit signals to control many cellular processes, including leukocyte migration. Gβγ signaling may regulate and be regulated by numerous signaling partners. Here, we reveal that WDR26, a member of the WD40 repeat protein family, directly bound free Gβγ in vitro, and formed a complex with endogenous Gβγ in Jurkat T cells stimulated by the chemokine SDF1α. Suppression of WDR26 by siRNAs selectively inhibited Gβγ-dependent phospholipase Cβ and PI3K activation, and attenuated chemotaxis in Jurkat T cells and differentiated HL60 cells in vitro and Jurkat T cell homing to lymphoid tissues in scid mice. Similarly, disruption of the WDR26/Gβγ interaction via expression of a WDR26 deletion mutant impaired Gβγ signaling and Jurkat T cell migration, indicating that the function of WDR26 depends on its binding to Gβγ. Additional data show that WDR26 also controlled RACK1, a negative regulator, in binding Gβγ and inhibiting leukocyte migration. Collectively, these experiments identify WDR26 as a novel Gβγ-binding protein that is required for the efficacy of Gβγ signaling and leukocyte migration.
authors: Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242.
authors: Zhizeng
authors: Z
authors: Sun
authors: Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242.
authors: Xiaoyun
authors: X
authors: Tang
authors: Departments of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242.
authors: Fang
authors: F
authors: Lin
authors: Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242; Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242. Electronic address: songhai-chen@uiowa.edu.
authors: Songhai
authors: S
authors: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002465:Cell Movement; D002633:Chemotaxis; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry*; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry*; D018922:HL-60 Cells; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000502:physiology*; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; C543172:WDR26 protein, human; C570115:WDR26 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins