Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals

  • FEBS Lett. 2021 Jun;595(11):1542-1558. doi: 10.1002/1873-3468.14083.
Jing Yang  1 ,  Tetsuya Hirata  2  3 ,  Yi-Shi Liu  1 ,  Xin-Yu Guo  1 ,  Xiao-Dong Gao  1 ,  Taroh Kinoshita  4  5 ,  Morihisa Fujita  1
Affiliations
  • 1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
  • 2. Institute for Glyco-core Research (iGCORE), Gifu University, Japan.
  • 3. Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University, Japan.
  • 4. Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • 5. WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
PMID: 33838053 DOI: 10.1002/1873-3468.14083
Abstract

Over 100 glycosylphosphatidylinositol-anchored proteins (GPI-APs) are encoded in the mammalian genome. It is not well understood how these proteins are targeted and translocated to the endoplasmic reticulum (ER). Here, we reveal that many GPI-APs, such as CD59, CD55, and CD109, utilize human SND2 (hSND2)-dependent ER targeting machinery. We also found that signal recognition particle receptors seem to cooperate with hSND2 to target GPI-APs to the ER. Both the N-terminal signal sequence and C-terminal GPI attachment signal of GPI-APs contribute to ER targeting via the hSND2-dependent pathway. Particularly, the hydrophobicity of the C-terminal GPI attachment signal acts as the determinant of hSND2 dependency. Our results explain the route and mechanism of the ER targeting of GPI-APs in mammalian cells.

Keywords
SND2; endoplasmic reticulum; glycosylphosphatidylinositol; protein targeting; signal recognition particle.
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