Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways
Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways
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DOI：
10.1007/s11302-011-9237-8
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发表时间：
2011-12-01
影响因子：
3.5
通讯作者：
Inoue, Kazuhide
中科院分区：
文献类型：
--
作者：
Kataoka, Ayako;Koga, Yui;Inoue, Kazuhide
小胶质细胞是中枢神经系统中的主要免疫活性细胞，具有高度的动态运动性。允许这些细胞移动的过程，如趋化和吞噬，被认为是它们功能的一部分，与嘌呤能信号密切相关。先前，我们报道了UDP刺激激活小胶质细胞中的P2Y(6)受体可以引起细胞的动态运动，从而增强其吞噬能力，正如小泉等人所报道的那样。(自然446(7139)：1091-1095,2007)。这些反应需要肌动蛋白细胞骨架重排，这是在UDP刺激后看到的。然而，细胞内信号转导途径尚未明确。在本研究中，我们发现在原代培养的大鼠小胶质细胞中，UDP能迅速诱导血管扩张剂刺激的磷酸蛋白(VASP)在Ser157位的瞬时磷酸化。VASP是肌动蛋白结合蛋白中的一种，它聚集在细胞膜上，其中丝状(F)-肌动蛋白以时间依赖的方式聚集。抑制PKC可抑制Vasp的磷酸化。UDP诱导的局部肌动蛋白聚集也被PKC抑制剂取消。Rho抑制剂CT04和抑制G(12/13)信号转导的p115-RGS的表达减弱了UDP诱导的Vasp的磷酸化和肌动蛋白聚集。这些结果表明，依赖于PKC和Rho的Vasp磷酸化参与了UDP诱导的小胶质细胞肌动蛋白聚集。
Microglia are major immunocompetent cells in the central nervous system and retain highly dynamic motility. The processes which allow these cells to move, such as chemotaxis and phagocytosis, are considered part of their functions and are closely related to purinergic signaling. Previously, we reported that the activation of the P2Y(6) receptor by UDP stimulation in microglia evoked dynamic cell motility which enhanced their phagocytic capacity, as reported by Koizumi et al. (Nature 446(7139):1091-1095, 2007). These responses require actin cytoskeletal rearrangement, which is seen after UDP stimulation. However, the intracellular signaling pathway has not been defined. In this study, we found that UDP in rat primary microglia rapidly induced the transient phosphorylation at Ser157 of vasodilator-stimulated phosphoprotein (VASP). VASP, one of actin binding protein, accumulated at the plasma membrane where filamentous (F)-actin aggregated in a time-dependent manner. The phosphorylation of VASP was suppressed by inhibition of PKC. UDP-induced local actin aggregations were also abrogated by PKC inhibitors. The Rho inhibitor CT04 and the expression of p115-RGS, which suppresses G(12/13) signaling, attenuated UDP-induced phosphorylation of VASP and actin aggregation. These results indicate that PKC- and Rho-dependent phosphorylation of VASP is involved in UDP-induced actin aggregation of microglia.