title: SNX17 affects T cell activation by regulating TCR and integrin recycling.
abstract: A key component in T cell activation is the endosomal recycling of receptors to the cell surface, thereby allowing continual integration of signaling and Ag recognition. One protein potentially involved in TCR transport is sorting nexin 17 (SNX17). SNX proteins have been found to bind proteins involved in T cell activation, but specifically the role of SNX17 in receptor recycling and T cell activation is unknown. Using immunofluorescence, we find that SNX17 colocalizes with TCR and localizes to the immune synapse in T- conjugates. Significantly, knockdown of the SNX17 resulted in fewer T-APC conjugates, lower CD69, TCR, and LFA-1 surface expression, as well as lower overall TCR recycling compared with control T cells. Lastly, we identified the 4.1/ezrin/radixin/moesin domain of SNX17 as being responsible in the binding and trafficking of TCR and LFA-1 to the cell surface. These data suggest that SNX17 plays a role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905;Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905; andDivision of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Osborne
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905;Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905; andDivision of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Piotrowski
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905;Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905; andDivision of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Dick
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905;Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905; andDivision of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905.
authors.forename: Jin-San
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905;Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905; andDivision of Oncology Research, Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905 billadeau.daniel@mayo.edu.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D059748:Proteolysis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016415:Sequence Alignment; D058305:Sorting Nexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; C487895:SNX17 protein, human; D058305:Sorting Nexins
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