title: Diacylglycerol kinase α regulates tubular recycling endosome biogenesis and major histocompatibility complex class I recycling.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Fred and Pamela Buffett Cancer Center, The University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology and the Fred and Pamela Buffett Cancer Center, The University of Nebraska Medical Center, Omaha, Nebraska 68198. Electronic address: nnaslavsky@unmc.edu.
authors.forename: Naava
authors.initials: N
authors.lastname: Naslavsky
authors.affiliation: Department of Biochemistry and Molecular Biology and the Fred and Pamela Buffett Cancer Center, The University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Steve
authors.initials: S
authors.lastname: Caplan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017951:Antigen Presentation; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003720:Densitometry; D019852:Diacylglycerol Kinase / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D010712:Phosphatidic Acids / Q000737:chemistry; D011485:Protein Binding; D021381:Protein Transport; D000096985:Calponins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002966:Clathrin; D003598:Cytoskeletal Proteins; D019852:Diacylglycerol Kinase; D015395:Histocompatibility Antigens Class I; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D010712:Phosphatidic Acids; C455272:MICAL1 protein, human; D000096985:Calponins
keywords: Clathrin-independent Endocytosis; Diacylglycerol Kinase; Endocytosis; Intracellular Trafficking; Major Histocompatibility Complex Class I; Membrane Trafficking; Phosphatidic Acid; Receptor Recycling; Structured Illumination Microscopy; Tubular Recycling Endosome