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首页> 外文期刊>Bioscience Reports >Both Intra- and Extracellular Ca2+ Participate in the Regulation of the Lateral Diffusion of the PDGF-β2 Receptor
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Both Intra- and Extracellular Ca2+ Participate in the Regulation of the Lateral Diffusion of the PDGF-β2 Receptor

机译：细胞内和细胞外Ca2 +均参与PDGF-β2受体横向扩散的调节

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When the receptors for platelet-derived growth factor (PDGF) are activatedthey aggregate, become tyrosine-phosphorylated and elicit a cascade ofdown-stream signals, including mobilization of Ca2+ from intra- andextracellular stores. Receptor mobility in the plane of the membrane isa prerequisite for receptor aggregation and further signalling. Using humanforeskin fibroblasts (AG 1523) and fluorescence recovery afterphotobleaching (FRAP), we therefore assessed the lateral mobilitycharacteristics of PDGF-β2 receptors by their diffusioncoefficient (D), and fraction of mobile receptors (R). This was done oncells stimulated with either normal human serum (NHS) or PDGF underdifferent Ca2+-conditions.The results suggest that both intra- and extracellular free Ca2+influence the mobility characteristics of the PDGF-β2receptor. Interestingly, the extracellular Ca2+ seems to imposegeneral restrictions on the mobility of receptors, since R increased whenextracellular Ca2+ was quenched with EGTA, whereas intracellularclamping of Ca2+ transients with MABTAM (BAPT/AM) primarily affectedD. When both intra- and extracellular Ca2+ were quenced, D remainedlow and R high, further supporting the proposition that they achievedistinct effects. Inhibition of tyrosine phosphorylation with Erbstatin,partly inhibited the NHS effects and released PDGF-induced receptorimmobilization. Ratio imaging with Fura-2 displayed that both NHS and PDGFinduced changes in intracellular free [Ca2+]. In view of the presentdata it might have important effects on the state of the receptor in themembrane, for instance by regulating its lateral mobility, communicationwith other receptors and signalling functions in the membrane.
机译：当血小板衍生生长因子（PDGF）的受体被激活时，它们就会聚集，酪氨酸磷酸化并引发一系列下游信号，包括从细胞内和细胞外储库中动员Ca2 +。膜平面内的受体迁移率是受体聚集和进一步发出信号的先决条件。因此，我们使用人包皮成纤维细胞（AG 1523）和光漂白后的荧光恢复（FRAP），通过PDGF-β2受体的扩散系数（D）和移动受体的分数（R）评估了PDGF-β2受体的侧向迁移特性。这是在不同Ca2 +条件下用正常人血清（NHS）或PDGF刺激的细胞上完成的。结果表明，细胞内和细胞外游离Ca2 +都影响PDGF-β2受体的迁移特性。有趣的是，由于细胞外Ca2 +被EGTA淬灭时R升高，因此细胞外Ca2 +似乎对受体的移动性施加了一般性的限制，而MABTAM（BAPT / AM）引起的细胞内Ca2 +瞬态的钳位则主要影响D。当细胞内和细胞外的Ca2 +都被抑制时，D保持较低而R保持较高，进一步支持了它们取得明显效果的主张。 Erbstatin抑制酪氨酸磷酸化，部分抑制NHS作用并释放PDGF诱导的受体固定化。用Fura-2进行比例成像显示NHS和PDGF均可诱导细胞内游离[Ca2 +]的变化。鉴于目前的数据，它可能对膜中受体的状态产生重要影响，例如通过调节其横向迁移率，与其他受体的通讯以及膜中的信号传导功能。

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