Brugnoli Federica, Bavelloni Alberto, Benedusi Mascia, Capitani Silvano, Bertagnolo Valeria
Signal Transduction Unit, Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy.
Cell Signal. 2007 Aug;19(8):1701-12. doi: 10.1016/j.cellsig.2007.03.007. Epub 2007 Mar 28.
During both maturation and function, neutrophils are subjected to reorganization of the actin cytoskeleton. Among the molecules that influence cytoskeletal architecture, the amount and subcellular localization of phosphoinositides, regulated by specific kinases and phosphatases, may play a crucial role. In neutrophils, PLC-beta2 is a major phosphoinositide-dependent phospholipase C isoform activated in response to chemoattractants, even though its role in the modifications of cell morphology and motility that occur during the inflammatory process has not been fully elucidated. In APL-derived promyelocytes induced to complete their maturation program, we have found that the expression levels of PLC-beta2 positively correlate with the degree of the reached neutrophil differentiation. Here, we demonstrate that PLC-beta2 modulates the migration capability of promyelocytes induced to differentiate with ATRA. In differentiating cells, the association of PLC-beta2 with actin, mediated by the PH domain, seems crucial for catalytic activity. We conclude that phosphodiesterase activity of PLC-beta2 on the actin-associated PIP2 may be responsible, by modifying the phosphoinositide pools, for the modifications of cytoskeleton architecture that take place during motility of differentiating promyelocytes.
在成熟和发挥功能的过程中,中性粒细胞都会经历肌动蛋白细胞骨架的重组。在影响细胞骨架结构的分子中,由特定激酶和磷酸酶调节的磷酸肌醇的数量和亚细胞定位可能起着关键作用。在中性粒细胞中,PLC-β2是一种主要的磷酸肌醇依赖性磷脂酶C同工型,可响应趋化因子而被激活,尽管其在炎症过程中发生的细胞形态和运动改变中的作用尚未完全阐明。在诱导完成成熟程序的急性早幼粒细胞白血病(APL)来源的早幼粒细胞中,我们发现PLC-β2的表达水平与达到的中性粒细胞分化程度呈正相关。在此,我们证明PLC-β2调节经全反式维甲酸(ATRA)诱导分化的早幼粒细胞的迁移能力。在分化细胞中,由PH结构域介导的PLC-β2与肌动蛋白的结合似乎对催化活性至关重要。我们得出结论,PLC-β2对与肌动蛋白相关的磷脂酰肌醇-4,5-二磷酸(PIP2)的磷酸二酯酶活性,可能通过修饰磷酸肌醇池,导致在分化早幼粒细胞运动过程中发生的细胞骨架结构改变。