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^*

^*Corresponding author for this work

Institute of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

39 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 language	English
Pages (from-to)	503-511
Number of pages	9
Journal	Nature Immunology
Volume	11
Issue number	6
DOIs	https://doi.org/10.1038/ni.1868
State	Published - Jun 2010

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10.1038/ni.1868

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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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doi = "10.1038/ni.1868",

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AU - Phee, Hyewon

AU - Dzhagalov, Ivan

AU - Mollenauer, Marianne

AU - Wang, Yana

AU - Irvine, Darrell J.

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.).

PY - 2010/6

Y1 - 2010/6

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.

AB - 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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JO - Nature Immunology

JF - Nature Immunology

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Regulation of thymocyte positive selection and motility by GIT2

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