title: Translocation dynamics of sorting nexin 27 in activated T cells.
abstract: Sorting nexin 27 (SNX27) belongs to the sorting nexin family of proteins, which participate in vesicular and protein trafficking. Similarly to all sorting nexin proteins, SNX27 has a functional PX domain that is important for endosome binding, but it is the only sorting nexin with a PDZ domain. We identified SNX27 as a partner of diacylglycerol kinase ζ (DGKζ), a negative regulator of T cell function that metabolises diacylglycerol to yield phosphatidic acid. SNX27 interacts with the DGKζ PDZ-binding motif in early/recycling endosomes in resting T cells; however, the dynamics and mechanisms underlying SNX27 subcellular localisation during T cell activation are unknown. We demonstrate that in T cells that encounter pulsed antigen-presenting cells, SNX27 in transit on early/recycling endosomes polarise to the immunological synapse. A fraction of SNX27 accumulates at the mature immunological synapse in a process that is dependent on vesicular trafficking, binding of the PX domain to phosphatidylinositol 3-phosphate and the presence of the PDZ region. Downmodulation of expression of either SNX27 or DGKζ results in enhanced basal and antigen-triggered ERK phosphorylation. These results identify SNX27 as a PDZ-containing component of the T cell immunological synapse, and demonstrate a role for this protein in the regulation of the Ras-ERK pathway, suggesting a functional relationship between SNX27 and DGKζ.
authors.affiliation: Lipid signalling Laboratory, Centro Nacional de Biotecnología/CSIC, E-28049 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Rincón
authors.forename: Julia
authors.initials: J
authors.lastname: Sáez de Guinoa
authors.forename: Severine I
authors.initials: SI
authors.lastname: Gharbi
authors.forename: Carlos O S
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Carrasco
authors.forename: Isabel
authors.initials: I
authors.lastname: Mérida
mesh_terms: D019852:Diacylglycerol Kinase / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D021381:Protein Transport / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C522885:SNX27 protein, human; D058305:Sorting Nexins; C526463:DGKZ protein, human; D019852:Diacylglycerol Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins