Regulation of thymocyte positive selection and motility by GIT2.
Regulation of thymocyte positive selection and motility by GIT2.
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胸腺细胞是一种高度活跃的细胞，随着它们的成熟，它们会在不同胸腺间隔内的趋化因子的影响下迁移。胸腺细胞的运动性受到严格的调控；然而，控制胸腺细胞运动性的分子机制还不是很清楚。在此，我们报告了G蛋白偶联受体激酶相互作用因子2(GIT2)是有效的阳性选择所必需的。有趣的是，GIT2−/−双阳性(DP)胸腺细胞在体外表现出更高的RAC活性，肌动蛋白聚合和向SDF-1和CCL25迁移。利用双光子激光扫描显微镜，我们发现胸腺皮质中GIT2−/−胸腺细胞的扫描活性严重受损，提示GIT2在调节趋化因子介导的DP胸腺细胞的运动中起关键作用。
Thymocytes are highly motile cells that migrate under the influence of chemokines in distinct thymic compartments as they mature. The motility of thymocytes is tightly regulated; however, the molecular mechanisms that control thymocyte motility are not well understood. Herein, we report that G protein-coupled receptor kinase-interactor 2 (GIT2) is required for efficient positive selection. Interestingly, GIT2−/− double positive (DP) thymocytes display increased Rac activation, actin polymerization and migration towards SDF-1 and CCL25 in vitro. Using two-photon laser scanning microscopy, we found that scanning activity of GIT2−/− thymocytes is severely compromised in the thymic cortex, suggesting GIT2 plays a key role in regulating chemokine-mediated motility of DP thymocytes.