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Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells
Published on: September 14, 2016
G protein-coupled receptor-mediated membrane targeting of PLCγ2 is essential for neutrophil chemotaxis
Xuehua Xu1, Xi Wen1, Smit Bhimani1
1Chemotaxis Signaling Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20850, United States.
Abstract:
The current dogma is that chemoattractants G protein-coupled receptors activate β phospholipase C while receptor tyrosine kinases activate γ phospholipase C. Here, we show that chemoattractant/G protein-coupled receptor-mediated membrane recruitment of γ2 phospholipase C constitutes G protein-coupled receptor-mediated phospholipase C signaling and is essential for neutrophil polarization and migration during chemotaxis. In response to a chemoattractant stimulation, cells lacking γ2 phospholipase C (plcg2kd) displayed altered dynamics of diacylglycerol production and calcium response, increased Ras/PI3K/Akt activation, elevated GSK3 phosphorylation and cofilin activation, impaired dynamics of actin polymerization, and, consequently, defects in cell polarization and migration during chemotaxis. The study reveals a molecular mechanism of membrane targeting of γ2 phospholipase C and the signaling pathways by which γ2 phospholipase C plays an essential role in neutrophil chemotaxis.
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