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Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation

Author

Listed:
  • Yicheng Wang

    (Osaka University
    Osaka University)

  • Yusuke Maeda

    (Osaka University)

  • Yi-Shi Liu

    (Jiangnan University)

  • Yoko Takada

    (Osaka University)

  • Akinori Ninomiya

    (Osaka University)

  • Tetsuya Hirata

    (Osaka University
    Osaka University
    Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University)

  • Morihisa Fujita

    (Jiangnan University)

  • Yoshiko Murakami

    (Osaka University
    Osaka University)

  • Taroh Kinoshita

    (Osaka University
    Osaka University)

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids interact with each other in the mammalian plasma membranes, forming dynamic microdomains. How their interaction starts in the cells has been unclear. Here, based on a genome-wide CRISPR-Cas9 genetic screen for genes required for GPI side-chain modification by galactose in the Golgi apparatus, we report that β1,3-galactosyltransferase 4 (B3GALT4), the previously characterized GM1 ganglioside synthase, additionally functions in transferring galactose to the N-acetylgalactosamine side-chain of GPI. Furthermore, B3GALT4 requires lactosylceramide for the efficient GPI side-chain galactosylation. Thus, our work demonstrates previously unexpected functional relationships between GPI-anchored proteins and glycosphingolipids in the Golgi. Through the same screening, we also show that GPI biosynthesis in the endoplasmic reticulum (ER) is severely suppressed by ER-associated degradation to prevent GPI accumulation when the transfer of synthesized GPI to proteins is defective. Our data demonstrates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system.

Suggested Citation

  • Yicheng Wang & Yusuke Maeda & Yi-Shi Liu & Yoko Takada & Akinori Ninomiya & Tetsuya Hirata & Morihisa Fujita & Yoshiko Murakami & Taroh Kinoshita, 2020. "Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14678-2
    DOI: 10.1038/s41467-020-14678-2
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