Inhibitory receptor FcγRIIb mediates the effects of IgG on a phagosome acidification and a sequential dephosphorylation system comprising SHIPs and Inpp4a
Inhibitory receptor FcγRIIb mediates the effects of IgG on a phagosome acidification and a sequential dephosphorylation system comprising SHIPs and Inpp4a
复制标题
抑制性受体 FcγRIIb 介导 IgG 对吞噬体酸化和包含 SHIP 和 Inpp4a 的连续去磷酸化系统的影响
作者：
Tomohiro Segawa;K. Hazeki;K. Nigorikawa;Atsuko Nukuda;Tomoki Tanizawa;K. Miyamoto;Shin Morioka;O. Hazeki
肌醇磷脂(PI)在吞噬体膜上的相对丰度随着吞噬过程的变化而变化。PtdIns(3，4，5)P3和PtdIns(3，4)P2在吞噬杯形成过程中迅速增加，密封后消失。在本研究中，我们使用Akt的增强型绿色荧光蛋白融合Pleckstrin同源结构域来监测这些PI物种的清除情况，Akt是一个结合原始264.7巨噬细胞中PtdIns(3，4，5)P3和PtdIns(3，4)P2的荧光探针。当吞噬颗粒包被免疫球蛋白时，PI的清除速度更快。在免疫球蛋白受体FcγRIIb缺陷的巨噬细胞中，未观察到免疫球蛋白的作用。为了确定与FcγRIIb加速PI清除有关的脂磷酸酶，我们制备了一组脂磷酸酶缺陷细胞。缺少PI 5-磷酸酶SrC同源2结构域包含肌醇-5-磷酸酶(SHIP)1或SHIP2会损害FcγRIIb加速的PI清除。PI4-磷酸酶Inpp4a的缺失也损害了Pis的加速清除。在FcγRIIb和Inpp4a缺陷细胞中，形成的吞噬小体的酸化速度减慢。这些结果表明，FcγRIIb驱动由SHIPS和Inpp4a组成的顺序去磷酸化系统，并加速吞噬小体的酸化。
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in the forming of the phagocytic cup, following which they disappear after sealing of the cup. In the present study, we monitored the clearance of these PI species using the enhanced green fluorescent protein-fused pleckstrin homology domain of Akt, a fluorescence probe that binds both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages. The clearance of PIs was much faster when the phagocytosed particles were coated with IgG. The effect of IgG was not observed in the macrophages deficient in FcγRIIb, an inhibitory IgG receptor. To identify the lipid phosphatases responsible for the FcγRIIb-accelerated PI clearance, we prepared a panel of lipid phosphatase-deficient cells. The lack of a PI 5-phosphatase Src homology 2 domain-containing inositol-5-phosphatase (SHIP)1 or SHIP2 impaired the FcγRIIb-accelerated clearance of PIs. The lack of a PI 4-phosphatase Inpp4a also impaired the accelerated PIs clearance. In the FcγRIIb- and Inpp4a-deficient cells, acidification of the formed phagosome was slowed. These results suggested that FcγRIIb drives the sequential dephosphorylation system comprising SHIPs and Inpp4a, and accelerates phagosome acidification.
非吞噬性 Fcgamma 受体抑制 Fcgamma 受体介导的吞噬作用。
影响因子：
20.3
作者：
Hunter,S;Indik,ZK;Kim,MK;Cauley,MD;Park,JG;Schreiber,AD
通讯作者：
Schreiber,AD
通过亲和洗脱色谱分离的肌醇多磷酸 4-磷酸酶水解磷脂酰肌醇 3,4-二磷酸。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Norris,FA;Majerus,PW
通讯作者：
Majerus,PW
影响因子：
20.3
作者：
Kim, JS;Peng, XD;Durden, DL
通讯作者：
Durden, DL