The extracellular domain of mGluR6 regulates targeting to the conventional secretion pathway
Bibliographic record
Abstract
In the retina, rod and cone photoreceptors relay information to bipolar cells at glutamatergic synapses. At dendritic tips of ON-type bipolar cells, which depolarize in response to light, the metabotropic glutamate receptor mGluR6 is required for neurotransmitter detection. mGluR6 also has a critical interaction with the presynaptic cell adhesion molecule ELFN1, and N-linked glycosylation of mGluR6 is required for this interaction. In the retina and in heterologous cells, mGluR6 undergoes conventional secretory trafficking with complex glycosylation acquired in the Golgi. However, the mechanisms regulating mGluR6 secretory trafficking are poorly understood. Like other class C GPCRs, mGluR6 has a large extracellular domain, which includes a bi-lobed ligand binding domain. We show that a series of small deletions in the upper lobe of the ligand-binding domain led to exclusive use of unconventional secretion and plasma membrane insertion of immature core-glycosylated protein in heterologous cells. Deletion of larger regions partially restored Golgi trafficking and complex glycosylation. The mutants with large deletions also exhibited dramatically increased plasma membrane localization, which was not recapitulated in the panel of mutants with small deletions. A large deletion did not prevent constitutive internalization, suggesting the increase in plasma membrane protein is due to forward trafficking flux. The results indicate an important role of the upper lobe of the ligand binding domain in regulating mGluR6 secretory trafficking, and suggest that disruption of the structure of this domain leads to unconventional trafficking. These findings are consistent with an intraluminal interaction regulating mGluR6 sorting within the endoplasmic reticulum. • Small deletions in the ligand-binding domain of mGluR6 lead to unconventional trafficking and plasma membrane insertion of immature core glycosylated protein • Larger deletions partially rescue Golgi trafficking and complex glycosylation, leading to plasma membrane insertion of both complex and core glycosylated protein • Large deletions in the ligand-binding domain confer dramatic increases in plasma membrane localization
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".