title: Xkr8 phospholipid scrambling complex in apoptotic phosphatidylserine exposure.
abstract: Xk-related protein (Xkr) 8, a protein carrying 10 transmembrane regions, is essential for scrambling phospholipids during apoptosis. Here, we found Xkr8 as a complex with basigin (BSG) or neuroplastin (NPTN), type I membrane proteins in the Ig superfamily. In BSG(-/-)NPTN(-/-) cells, Xkr8 localized intracellularly, and the apoptosis stimuli failed to expose phosphatidylserine, indicating that BSG and NPTN chaperone Xkr8 to the plasma membrane to execute its scrambling activity. Mutational analyses of BSG showed that the atypical glutamic acid in the transmembrane region is required for BSG's association with Xkr8. In cells exposed to apoptotic signals, Xkr8 was cleaved at the C terminus and the Xkr8/BSG complex formed a higher-order complex, likely to be a heterotetramer consisting of two molecules of Xkr8 and two molecules of BSG or NPTN, suggesting that this cleavage causes the formation of a larger complex of Xkr8-BSG/NPTN for phospholipid scrambling.
authors: Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors: Jun
authors: J
authors: Suzuki
authors: Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors: Eiichi
authors: E
authors: Imanishi
authors: Laboratory of Biochemistry and Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan snagata@ifrec.osaka-u.ac.jp.
authors: Shigekazu
authors: S
authors: Nagata
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D051926:Basigin / Q000172:deficiency / Q000235:genetics*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000494:pharmacology; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis
chemical_list: D051017:Apoptosis Regulatory Proteins; C497886:BSG protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C518360:NPTN protein, human; D010718:Phosphatidylserines; C582783:Xkr8 protein, human; D051926:Basigin; D018698:Glutamic Acid
keywords: Xkr8; basigin; chaperone; neuroplastin; phospholipid scramblase