Diacylglycerol kinase zeta is a member of the diacylglycerol kinase family of 
enzymes, which generate phosphatidic acid through diacylglycerol 
phosphorylation. In addition to the catalytic and cysteine-rich domains found in 
all diacylglycerol kinases, diacylglycerol kinase zeta has a MARCKS domain as 
well as a C-terminal region containing four ankyrin repeats and a PDZ-binding 
motif. Previous reports demonstrated that diacylglycerol kinase zeta interaction 
with several proteins is an important mechanism for modulating the localization 
and activity of this enzyme. Here we used a proteomics approach to search for 
novel diacylglycerol kinase zeta-interacting proteins and identified sorting 
nexin 27 (SNX27), a recently described member of a protein family involved in 
intracellular trafficking, which has a PDZ domain in addition to the phox 
homology domain characteristic of SNX proteins. Co-immunoprecipitation studies 
and two-hybrid analysis confirmed physical, PDZ-dependent association between 
SNX27 and diacylglycerol kinase zeta. Because diacylglycerol kinase zeta is 
expressed abundantly in T lymphocytes, we characterized SNX27 expression and 
subcellular localization in these cells. SNX27 co-localized with transferrin 
receptor-positive vesicles, pointing to its participation in T cell endocytic 
recycling. Expression of deletion mutants revealed that in addition to the phox 
homology domain the SNX27 PDZ domain contributed to vesicle localization of this 
protein, suggesting that interaction with diacylglycerol kinase zeta regulates 
SNX27 localization. Analysis of cells with RNA interference-mediated knockdown 
of diacylglycerol kinase zeta showed accelerated transferrin receptor exit from 
the lymphocyte endocytic recycling compartment back to the plasma membrane, 
further confirming diacylglycerol kinase zeta-dependent control of vesicle 
trafficking. These data support a previously unreported role for diacylglycerol 
kinase zeta in the modulation of membrane trafficking, which may also help to 
define SNX27 function.