Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y(6) Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia
Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y(6) Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia
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蛋白质相互作用 C 激酶 1 调节小胶质细胞中 P2Y(6) 嘌呤受体、肌动蛋白聚合和吞噬作用的表面表达
DOI：
10.1007/s11064-015-1754-3
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发表时间：
2016
影响因子：
4.4
通讯作者：
Li Yun-Hong
中科院分区：
文献类型：
--
作者：
Zhu Jia;Wang Zhen;Zhang Nan;Ma Jiao;Xu Shui-Lin;Wang Yin;Shen Ying;Li Yun-Hong
小胶质细胞通过吞噬中枢神经系统来清除死亡的细胞和碎片。UDP激活的P2Y6受体诱导吞噬杯状结构的形成，并在吞噬过程中增加P2Y6R的表达。然而，目前还不清楚P2Y6R的表面表达是如何增加的。PICK1(与C-激酶-1相互作用的蛋白质)与多种神经递质受体、转运蛋白和酶相互作用。我们在这里报道了PICK1可能与P2Y6R相互作用。在PICK1基因敲除小鼠和PICK1基因敲除的BV2细胞中，小胶质细胞表面的P2Y6R减少，电生理记录也证实了这一点，表明在BV2小胶质细胞中，PICK1过表达增加了P2Y6R介导的电流，而PICK1基因敲除的BV2细胞则减少了P2Y6R介导的电流。最后，PICK1足以影响原代小胶质细胞和BV2细胞的细胞骨架聚集和吞噬功能。这些结果表明，PICK1是P2Y6R表达和小胶质细胞吞噬的重要调节因子。
Microglia clean up dead cells and debris through phagocytosis in the central nervous system. UDP-activated P2Y6receptors (P2Y6Rs) induce the formation of phagocytic cup-like structure and P2Y6R expression is increased during the phagocytosis. However, it remains unclear how surface expression of P2Y6R is increased. PICK1 (protein interacting with C-kinase-1) interacts with various neurotransmitter receptors, transporters, and enzymes. We here report that PICK1 might interact with P2Y6R. Surface P2Y6R was reduced in microglia from PICK1-knockout mice and PICK1-knockdown BV2 cells, which was also confirmed by electrophysiological recordings, showing that P2Y6R-mediated current was increased by PICK1 overexpression but was reduced by PICK1-knockdown in BV2 microglia. Finally, PICK1 was sufficient to affect cytoskeletal aggregation and phagocytosis both in primary microglia and BV2 cells. These results indicate that PICK1 is an important regulator of P2Y6R expression and microglial phagocytosis.