Journal article
WD40-repeat proteins control the flow of Gβγ signaling for directional cell migration
Cell adhesion & migration, Vol.7(2), pp.214-218
03/01/2013
DOI: 10.4161/cam.22940
PMCID: PMC3954032
PMID: 23302952
Abstract
The ability of cells to generate a highly polarized intracellular signal through G protein-coupled receptors (GPCRs) is essential for their migration toward chemoattractants. The Gβγ subunits of heterotrimeric G proteins play a critical role in transmitting chemotactic signals from GPCRs via the activation of diverse effectors, including PLCβ and PI3K, primarily at the leading edge of cells. Although Gβγ can directly activate many of these effectors through protein-protein interactions in vitro, it remains unclear how Gβγ spatially and temporally orchestrates the activation of these effectors in vivo. A yeast two-hybrid screen for Gβ interacting proteins identified two WD40-repeat domain containing proteins, RACK1 and WDR26, which are predicted to serve as scaffolding/adaptor proteins. Previous data indicates that RACK1 negatively regulates Gβγ-mediated leukocyte migration by inhibiting Gβγ-stimulated PLCβ and PI3K activities. In contrast, recently published work by Sun et al. indicates that WDR26 promotes leukocyte migration by enhancing Gβγ-mediated signal transduction. These findings reveal a novel mechanism regulating Gβγ signaling during chemotaxis, namely through the positive and negative regulation of WDR26 and RACK1 on Gβγ to promote and fine tune Gβγ-mediated effector activation, ultimately governing the ability of cells to polarize and migrate toward a chemoattractant gradient.
Details
- Title: Subtitle
- WD40-repeat proteins control the flow of Gβγ signaling for directional cell migration
- Creators
- Caitlin Runne - Department of Pharmacology; Roy J. and Lucille A. Carver College of Medicine; University of Iowa; Iowa City, IA USASonghai Chen - Department of Pharmacology; Roy J. and Lucille A. Carver College of Medicine; University of Iowa; Iowa City, IA USA
- Resource Type
- Journal article
- Publication Details
- Cell adhesion & migration, Vol.7(2), pp.214-218
- Publisher
- Landes Bioscience
- DOI
- 10.4161/cam.22940
- PMID
- 23302952
- PMCID
- PMC3954032
- ISSN
- 1933-6918
- eISSN
- 1933-6926
- Language
- English
- Date published
- 03/01/2013
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040455702771
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