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Regulation of thymocyte positive selection and motility by GIT2.

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.

SUBMITTER: Phee H

PROVIDER: S-EPMC3620668 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Regulation of thymocyte positive selection and motility by GIT2.

Phee Hyewon H Dzhagalov Ivan I Mollenauer Marianne M Wang Yana Y Irvine Darrell J DJ Robey Ellen E Weiss Arthur A

Nature immunology 20100502 6

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 polyme ...[more]

PMID: 20431621

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