%0 Journal Article
%T G protein-coupled receptor-mediated membrane targeting of PLCγ2 is essential for neutrophil chemotaxis.
%A Xu X
%A Wen X
%A Bhimani S
%A Moosa A
%A Parsons D
%A Ha H
%A Jin T
%J J Leukoc Biol
%V 114
%N 2
%D Jul 2023 27
%M 37040618
%F 6.011
%R 10.1093/jleuko/qiad043
%X 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.