RRC ID 67356
Author Suzuki J, Imanishi E, Nagata S.
Title Xkr8 phospholipid scrambling complex in apoptotic phosphatidylserine exposure.
Journal Proc Natl Acad Sci U S A
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.
Volume 113(34)
Pages 9509-14
Published 2016-8-23
DOI 10.1073/pnas.1610403113
PII 1610403113
PMID 27503893
PMC PMC5003272
MeSH Apoptosis / drug effects Apoptosis / genetics* Apoptosis Regulatory Proteins / genetics* Apoptosis Regulatory Proteins / metabolism Basigin / deficiency Basigin / genetics* Biological Transport Cell Line, Tumor Cell Membrane / chemistry Cell Membrane / drug effects Cell Membrane / metabolism* Fas Ligand Protein / pharmacology Gene Expression Glutamic Acid / metabolism Humans Leukocytes / chemistry Leukocytes / drug effects Leukocytes / metabolism Membrane Glycoproteins / deficiency Membrane Glycoproteins / genetics* Membrane Proteins / genetics* Membrane Proteins / metabolism Mutation Phosphatidylserines / chemistry Phosphatidylserines / metabolism* Protein Binding Proteolysis
IF 9.412
DNA material pCX4-mBSG-c-HA (273) (RDB18961) pCX4-mBSG-c-HA (389) (RDB18962) pCX4-mNPTN-c-HA (281) (RDB18963) pCX4-mNPTN-c-HA (397) (RDB18964) pCX4-mEMB-c-HA (330) (RDB18965) pCX4-hBSG-c-HA (269) (RDB18966) pCX4-hBSG-c-HA (385) (RDB18967) pCX4-hNPTN-c-HA (282) (RDB18968) pCX4-hNPTN-c-HA (398) (RDB18969)