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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Apoptosis
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Calcium / metabolism
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Cell Cycle Proteins / genetics*
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Cell Movement*
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Cells, Cultured
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Chemokine CXCL12 / metabolism
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Chemokines, CC / metabolism
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Down-Regulation
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Fluorescent Antibody Technique
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GTPase-Activating Proteins
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Intercellular Signaling Peptides and Proteins
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Neuropeptides / metabolism
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Phosphoproteins / genetics*
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Selection, Genetic*
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Thymus Gland / cytology*
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Thymus Gland / metabolism
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rac GTP-Binding Proteins / metabolism
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rac1 GTP-Binding Protein
Substances
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Ccl25 protein, mouse
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Cell Cycle Proteins
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Chemokine CXCL12
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Chemokines, CC
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GTPase-Activating Proteins
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Git2 protein, mouse
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Intercellular Signaling Peptides and Proteins
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Neuropeptides
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Phosphoproteins
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Rac1 protein, mouse
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Extracellular Signal-Regulated MAP Kinases
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein
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Calcium