Regulation of thymocyte positive selection and motility by GIT2.
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.
Phee
Hyewon
H
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Dzhagalov
Ivan
I
Mollenauer
Marianne
M
Wang
Yana
Y
Irvine
Darrell J
DJ
Robey
Ellen
E
Weiss
Arthur
A
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
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