The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration

Zhizeng Sun; Xiaoyun Tang; Fang Lin; Songhai Chen

doi:10.1074/jbc.M111.301382

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The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration

Journal article

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Peer reviewed

The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration

Zhizeng Sun, Xiaoyun Tang, Fang Lin and Songhai Chen

The Journal of biological chemistry, Vol.286(51), pp.43902-43912

12/23/2011

DOI: 10.1074/jbc.M111.301382

PMCID: PMC3243526

PMID: 22065575

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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.

Proteins - physiology

GTP-Binding Protein gamma Subunits - chemistry

Receptors, G-Protein-Coupled - metabolism

Signal Transduction

Jurkat Cells

Humans

Mice, SCID

Chemotaxis

GTP-Binding Protein beta Subunits - chemistry

Animals

Intracellular Signaling Peptides and Proteins - chemistry

HL-60 Cells

Heterotrimeric GTP-Binding Proteins - chemistry

Protein Binding

Mice

Proteins - chemistry

Intracellular Signaling Peptides and Proteins - physiology

Cell Movement

Leukocytes - cytology

Details

Title: Subtitle: The WD40 repeat protein WDR26 binds Gβγ and promotes Gβγ-dependent signal transduction and leukocyte migration
Creators: Zhizeng Sun - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Xiaoyun Tang
Fang Lin
Songhai Chen
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.286(51), pp.43902-43912
DOI: 10.1074/jbc.M111.301382
PMID: 22065575
PMCID: PMC3243526
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: GM094255 / NIGMS NIH HHS R01 GM094255-01A1 / NIGMS NIH HHS R00 RR024119 / NCRR NIH HHS R01 GM094255 / NIGMS NIH HHS
Language: English
Date published: 12/23/2011
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984025666802771

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