1. Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals.
- Author
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Yang J, Hirata T, Liu YS, Guo XY, Gao XD, Kinoshita T, and Fujita M
- Subjects
- Antigens, CD genetics, Antigens, CD metabolism, Arsenite Transporting ATPases genetics, Arsenite Transporting ATPases metabolism, CD55 Antigens genetics, CD59 Antigens genetics, GPI-Linked Proteins genetics, GPI-Linked Proteins metabolism, Gene Expression, Glycosylphosphatidylinositols chemistry, HEK293 Cells, Humans, Hydrophobic and Hydrophilic Interactions, Membrane Proteins deficiency, Membrane Proteins metabolism, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Protein Binding, Protein Domains, Protein Sorting Signals, Protein Transport, SEC Translocation Channels genetics, CD55 Antigens metabolism, CD59 Antigens metabolism, Endoplasmic Reticulum metabolism, Glycosylphosphatidylinositols metabolism, Membrane Proteins genetics, SEC Translocation Channels metabolism
- 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., (© 2021 Federation of European Biochemical Societies.)
- Published
- 2021
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