title: 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.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Phee
authors.forename: Ivan
authors.initials: I
authors.lastname: Dzhagalov
authors.forename: Marianne
authors.initials: M
authors.lastname: Mollenauer
authors.forename: Yana
authors.initials: Y
authors.lastname: Wang
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
authors.forename: Ellen
authors.initials: E
authors.lastname: Robey
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics*; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics*; D012641:Selection, Genetic; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
chemical_list: C491541:Ccl25 protein, mouse; D018797:Cell Cycle Proteins; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D020690:GTPase-Activating Proteins; C120767:Git2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C484602:Rac1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D002118:Calcium