期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 34, 页码 9509-9514出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1610403113
关键词
phospholipid scramblase; Xkr8; chaperone; basigin; neuroplastin
资金
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology from Japan Agency for Medical Research and Development
- Precursory Research for Innovative Medical Care from Japan Agency for Medical Research and Development
- Grants-in-Aid for Scientific Research [15H05785, 15H05651] Funding Source: KAKEN
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.
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