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.