Regulation of thymocyte positive selection and motility by GIT2

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

doi:10.1038/ni.1868

Regulation of thymocyte positive selection and motility by GIT2

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

^*此作品的通信作者

微生物及免疫學研究所

研究成果: Article › 同行評審

39 引文斯高帕斯（Scopus）

摘要

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.

原文	English
頁（從 - 到）	503-511
頁數	9
期刊	Nature Immunology
卷	11
發行號	6
DOIs	https://doi.org/10.1038/ni.1868
出版狀態	Published - 6月 2010

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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.",

author = "Hyewon Phee and Ivan Dzhagalov and Marianne Mollenauer and Yana Wang and Irvine, {Darrell J.} and Ellen Robey and Arthur Weiss",

note = "Funding Information: We thank the Transgenic/Targeted Mutagenesis Core Facility of the University of California San Francisco Comprehensive Cancer Center for creating Git2−/− mice; the Biological Imaging Development Center of the University of California San Francisco for Imaris software support; and E. Manser (Institute of Molecular and Cell Biology, Singapore) for monoclonal and polyclonal antibodies that recognize the α-and β-isoforms of PIX. Supported by the Leukemia and Lymphoma Society (H.P.) and the National Institutes of Health (R01AI064227 to E.R.).",

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AU - Robey, Ellen

AU - Weiss, Arthur

N1 - Funding Information: We thank the Transgenic/Targeted Mutagenesis Core Facility of the University of California San Francisco Comprehensive Cancer Center for creating Git2−/− mice; the Biological Imaging Development Center of the University of California San Francisco for Imaris software support; and E. Manser (Institute of Molecular and Cell Biology, Singapore) for monoclonal and polyclonal antibodies that recognize the α-and β-isoforms of PIX. Supported by the Leukemia and Lymphoma Society (H.P.) and the National Institutes of Health (R01AI064227 to E.R.).

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N2 - 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.

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Regulation of thymocyte positive selection and motility by GIT2

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