新型SDF-1α受体CXCR7促进神经干细胞的抗凋亡和生存

神经系统炎症反应可激活病变部位和周围区域神经干细胞的神经再生。神经再生过程涉及到神经干细胞的生存，迁移和分化。SDF-1α结合CXCR4激活下游信号通路从而促进神经干细胞的生存和迁移。最近，对趋化因子SDF-1α的另一新型受体CXCR7的研究已成为热点，已有报道CXCR7影响神经干细胞的生存和迁移，并揭示CXCR7的作用与CXCR4密切相关。CXCR4和CXCR7在生理条件下可形成二聚体,提示受体之间的相互作用调节某种生理功能。我们将通过对CXCR7过表达，siCXCR7，CXCR4和CXCR7基因敲除鼠等技术的使用，阐明在SDF-1α介导下CXCR7对神经干细胞抗凋亡的作用；通过对SDF-1α介导的CXCR4/CXCR7相互作用的研究， 阐明CXCR7对SDF-1α/CXCR4通路的影响；并揭示CXCR7，作为一个非G蛋白依赖受体的生物学意义和应用的潜在价值。

Neuroinflammation activates neurogenesis of neural stem cells in neural injury regions and pathological areas of neurodegenerative diseases. SDF-1, a chemokine, also known as CXCL12, is widely expressed in the central nervous system (CNS). It is critical for human neual progenitor cells (hNPCs) migration through its receptor CXCR4 . Recently, CXCR7 has been found binding to CXCL12 with higher affinity than CXCR4. However, CXCR7 is not a common G-protein receptor, but may recruit beta-arrestin2 after CXCL12 treatment. Little is known about the function of CXCR7 in hNPCs. In addition, CXCR4 ad CXCR7 may form a heterodimer. In this project, we will base on the our former study which demonstrates that SDF-1 rescues apoptosis induced by starvation and camptothecin(CAMP) through both CXCR4 and CXCR7. Furthermore, we hypothesize that CXCR7 may play an independent critical role in anti-apoptosis and survival. The interaction of CXCR4 and CXCR7 may have special function via SDF-1 for cell apoptosis and survival. The hypothesis also involves in recruitment of beta-arrestin2 at early endosome, and function of beta-arrestin 2 as a scaffold protein to activate phosphorylation of AKT and ERK.