Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Nat Immunol. 2010 Jun;11(6):503-11. doi: 10.1038/ni.1868. Epub 2010 May 2.
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. Here we report that G protein-coupled receptor kinase-interactor 2 (GIT2) was required for efficient positive selection. Notably, Git2(-/-) double-positive thymocytes showed greater activation of the small GTPase Rac, actin polymerization and migration toward the chemokines CXCL12 (SDF-1) and CCL25 in vitro. By two-photon laser-scanning microscopy, we found that the scanning activity of Git2(-/-) thymocytes was compromised in the thymic cortex, which suggests GIT2 has a key role in regulating the chemokine-mediated motility of double-positive thymocytes.
胸腺细胞是高度能动的细胞,在成熟过程中会在趋化因子的影响下迁移到特定的胸腺区室中。胸腺细胞的迁移是受到严格调控的;然而,控制胸腺细胞迁移的分子机制尚不清楚。在这里,我们报告 G 蛋白偶联受体激酶相互作用蛋白 2(GIT2)对于有效阳性选择是必需的。值得注意的是,Git2(-/-)双阳性胸腺细胞表现出更高的小 GTPase Rac 的激活、肌动蛋白聚合以及向趋化因子 CXCL12(SDF-1)和 CCL25 的体外迁移。通过双光子激光扫描显微镜,我们发现 Git2(-/-)胸腺细胞在胸腺皮质中的扫描活性受损,这表明 GIT2 在调节双阳性胸腺细胞的趋化因子介导的迁移中具有关键作用。