Regulation of thymocyte positive selection and motility by GIT2

H Phee, I Dzhagalov, M Mollenauer, Y Wang… - Nature …, 2010 - nature.com
H Phee, I Dzhagalov, M Mollenauer, Y Wang, DJ Irvine, E Robey, A Weiss
Nature immunology, 2010nature.com
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 …
Abstract
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.
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