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.
摘要：
目前的教条是化学引诱物G蛋白偶联受体（GPCR）激活β磷脂酶C（PLCβ），而受体酪氨酸激酶（RTK）激活γ磷脂酶C（PLCγ）。这里,我们发现,趋化/GPCR介导的PLCγ2膜募集构成了GPCR介导的磷脂酶C(PLC)信号传导,对于趋化过程中的中性粒细胞极化和迁移至关重要.作为对化学引诱物刺激的反应，缺乏PLCγ2（plcg2kd）的细胞显示出二酰甘油（DAG）产生和钙反应的动力学改变；Ras/PI3K/Akt激活增加；GSK3磷酸化和cofilin激活升高；肌动蛋白聚合的动力学受损；因此，趋化过程中细胞极化和迁移的缺陷。该研究揭示了PLCγ2的膜靶向分子机制以及PLCγ2在中性粒细胞趋化中起重要作用的信号通路。
