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

Autor: Tetsuya Hirata, Yi-Shi Liu, Xiao-Dong Gao, Xin-Yu Guo, Morihisa Fujita, Taroh Kinoshita, Jing Yang
Rok vydání: 2021
Předmět:
Signal peptide
Glycosylphosphatidylinositols
Biophysics
Gene Expression
CD59 Antigens
CD59
Protein Sorting Signals
Endoplasmic Reticulum
GPI-Linked Proteins
medicine.disease_cause
Biochemistry
03 medical and health sciences
Protein Domains
Antigens
CD
Structural Biology
Protein targeting
Genetics
medicine
Humans
Receptor
Molecular Biology
030304 developmental biology
0303 health sciences
Signal recognition particle
Er targeting
CD55 Antigens
Chemistry
Arsenite Transporting ATPases
Endoplasmic reticulum
030302 biochemistry & molecular biology
Membrane Proteins
Cell Biology
Gpi anchored protein
Neoplasm Proteins
Cell biology
carbohydrates (lipids)
Protein Transport
HEK293 Cells
lipids (amino acids
peptides
and proteins)
Hydrophobic and Hydrophilic Interactions
SEC Translocation Channels
Protein Binding
Zdroj: FEBS Letters. 595:1542-1558
ISSN: 1873-3468
0014-5793
Popis: 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.
Databáze: OpenAIRE
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