| RRC ID |
89146
|
| Author |
Akagi T, Ogiwara I, Shimohata A, Takeda R, Sakamoto T, Kato D, Kaneda M.
|
| Title |
N-Glycosylation of mGluR6 Modulates Receptor Cell-Surface Transport, G-Protein Coupling, and Interactions With Synaptic Adhesion Molecules.
|
| Journal |
J Mol Neurosci
|
| Abstract |
Metabotropic glutamate receptor 6 (mGluR6) is a synaptic receptor expressed predominantly in retinal ON-bipolar cells. The N-terminal extracellular domain (ECD) of mGluR6 engages in ligand binding and also participates in mGluR6 cell-surface localization and trans-synaptic cell-adhesion complex formation. We herein investigated whether N-glycosylation in the mGluR6 ECD is involved in modulating receptor cell-surface transport, G-protein coupling, and interactions with Elfn1 and Lrit1 using 293T cells expressing ECD mutants with the asparagine-to-glutamine (N-to-Q) substitution in N-glycosylation sequons. The results obtained showed that mGluR6 underwent N-glycosylation at the asparagine residues N290, N445, N473, and N561 in the ECD, and the simultaneous blockage of N-glycosylation at these sites reduced cellular mGluR6 levels. Furthermore, mGluR6 cell-surface levels were decreased by N290Q and N445Q, but unaffected by N473Q and N561Q, while each N-to-Q substitution at the respective sites consistently impaired glutamate-induced G-protein-mediated responses. We also showed that mGluR6 was pulled down with Elfn1 in vitro, and coimmunoprecipitated with Lrit1 in co-transfected cells. The mGluR6-Elfn1 interaction was inhibited by N445Q and facilitated by N473Q and N561Q, whereas the mGluR6-Lrit1 interaction was promoted by N290Q and suppressed by N561Q. Collectively, these results indicate that each of the N-glycosylation sites contributed to efficient G-protein coupling, while the respective sites were involved in the modulation of receptor cell-surface transport and adhesion complex formation with Elfn1 and also with Lrit1 in distinct directions. Therefore, the N-glycosylation of synaptic receptors may have roles in modulating trans-synaptic bridge formation, potentially influencing the tuning of signal transmission.
|
| Volume |
76(2)
|
| Published |
2026-5-27
|
| DOI |
10.1007/s12031-026-02546-5
|
| PII |
10.1007/s12031-026-02546-5
|
| PMID |
42201444
|
| MeSH |
Animals
Cell Membrane / metabolism
Glycosylation
HEK293 Cells
Humans
Nerve Tissue Proteins / metabolism
Protein Transport
Receptors, Metabotropic Glutamate* / chemistry
Receptors, Metabotropic Glutamate* / genetics
Receptors, Metabotropic Glutamate* / metabolism
|
| IF |
2.678
|
| Resource |
| Human and Animal Cells |
293T(RCB2202) |
