Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions
| Autor: | Saki Yamamoto, Ryosuke Midorikawa, Motohiro Nonaka, Hiromu Takematsu, Kogo Takamiya, Jyoji Morise, Shogo Oka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Glycosylation Recombinant Fusion Proteins Green Fluorescent Proteins Mutant Cell Gene Expression AMPA receptor Article Catalysis Inorganic Chemistry Cell membrane Synapse lcsh:Chemistry 03 medical and health sciences 0302 clinical medicine medicine Humans AMPA-type glutamate receptor Physical and Theoretical Chemistry Protein Structure Quaternary N-Glycosylation Site Molecular Biology lcsh:QH301-705.5 Spectroscopy Ion channel Binding Sites Chemistry Cell Membrane Organic Chemistry Glutamate receptor General Medicine Computer Science Applications Cell biology GluA2 HEK293 Cells 030104 developmental biology medicine.anatomical_structure Amino Acid Substitution Receptors Glutamate lcsh:Biology (General) lcsh:QD1-999 Mutation N-glycan Mutagenesis Site-Directed 030217 neurology & neurosurgery GluA1 |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 5101, p 5101 (2020) International Journal of Molecular Sciences Volume 21 Issue 14 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1–4), and its abundance in the synapse determines the strength of synaptic activity. The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits’ ER-exit and translocation to the cell membrane. Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear. In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions. In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner. Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression. Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT. In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate. |
| Databáze: | OpenAIRE |
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