DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells.
DOCK2 is a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City which are known to regulate actin cytoskeleton. DOCK2 is critical for lymphocyte migration, yet the role of DOCK2 in TCR signaling remains unclear. We show here that DOCK2 is essential for TCR-mediated Rac activation and immunological synapse formation. In DOCK2-deficient T cells, antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, to the APC interface was severely impaired, resulting in a significant reduction of antigen-specific T cell proliferation. In addition, we found that the efficacy of both positive and negative selection was reduced in DOCK2-deficient mice. These results suggest that DOCK2 regulates T cell responsiveness through remodeling of actin cytoskeleton via Rac activation.
Sanui
Terukazu
T
Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
Inayoshi
Ayumi
A
Noda
Mayuko
M
Iwata
Eiko
E
Oike
Masahiro
M
Sasazuki
Takehiko
T
Fukui
Yoshinori
Y
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D002352:Carrier Proteins; C471356:DOCK2 protein, mouse; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D007527:Isoenzymes; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein