Regulation of thymocyte positive selection and motility by GIT2

Hyewon Phee, Ivan Dzhagalov, Marianne Mollenauer, Yana Wang, Darrell J. Irvine, Ellen Robey, Arthur Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish
Pages (from-to)503-511
Number of pages9
JournalNature Immunology
Volume11
Issue number6
DOIs
StatePublished - Jun 2010

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