Diacylglycerol Kinase α Regulates Tubular Recycling Endosome Biogenesis and Major Histocompatibility Complex Class I Recycling*
Diacylglycerol Kinase α Regulates Tubular Recycling Endosome Biogenesis and Major Histocompatibility Complex Class I Recycling*
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DOI：
10.1074/jbc.m114.594291
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Shuwei Xie;Naava Naslavsky;S. Caplan
中科院分区：
文献类型：
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作者：
Shuwei Xie;Naava Naslavsky;S. Caplan
Background: Major histocompatibility complex class I (MHC I) trafficking is crucial for antigen presentation. Results: Diacylglycerol kinase α (DGKα) depletion interferes with tubular recycling endosome (TRE) biogenesis and delays MHC I recycling to the plasma membrane. Conclusion: DGKα mediates MHC I recycling by interacting with MICAL-L1 and generating phosphatidic acid. Significance: A novel role for DGKα in generating phosphatidic acid for TRE biogenesis and MHC I recycling. Major histocompatibility complex class I (MHC I) presents intracellular-derived peptides to cytotoxic T lymphocytes and its subcellular itinerary is important in regulating the immune response. While a number of diacylglycerol kinase isoforms have been implicated in clathrin-dependent internalization, MHC I lacks the typical motifs known to mediate clathrin-dependent endocytosis. Here we show that depletion of diacylglycerol kinase α (DGKα), a kinase devoid of a clathrin-dependent adaptor protein complex 2 binding site, caused a delay in MHC I recycling to the plasma membrane without affecting the rate of MHC I internalization. We demonstrate that DGKα knock-down causes accumulation of intracellular and surface MHC I, resulting from decreased degradation. Furthermore, we provide evidence that DGKα is required for the generation of phosphatidic acid required for tubular recycling endosome (TRE) biogenesis. Moreover, we show that DGKα forms a complex with the TRE hub protein, MICAL-L1. Given that MICAL-L1 and the F-BAR-containing membrane-tubulating protein Syndapin2 associate selectively with phosphatidic acid, we propose a positive feedback loop in which DGKα generates phosphatidic acid to drive its own recruitment to TRE via its interaction with MICAL-L1. Our data support a novel role for the involvement of DGKα in TRE biogenesis and MHC I recycling.
