期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 5, 页码 776-788出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.072447
关键词
Sorting nexins; PDZ; Membrane trafficking; T cells; Immunological synapse; Diacylglycerol kinase
类别
资金
- Comunidad de Madrid [S-SAL-0311]
- Spanish Ministry of Health (Instituto de Salud Carlos III) [RD067002071035]
- Spanish Ministry of Education [BFU2007-62639]
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 zeta (DGK zeta), a negative regulator of T cell function that metabolises diacylglycerol to yield phosphatidic acid. SNX27 interacts with the DGK zeta 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 DGK zeta 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 DGK zeta.
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