TheN-Methyl-d-aspartate Receptor Splice Variant NR1–4 C-terminal Domain
Bibliographic record
Abstract
The intracellular C-terminal domain of the N-methyl-d-aspartate receptor (NMDAR) subunits 1 (NR1) and 2 (NR2) are important, if not essential, to the process of NMDAR clustering and anchoring at the plasma membrane and the synapse. Eight NR1 splice variants exist, four of which arise from alternative splicing of the C-terminal exon cassettes. Alternative splice variants may display a differential ability to interact with synaptic anchoring proteins, and splicing of C-terminal exon cassettes may alter the mechanism(s) of subcellular localization and targeting. The NR1-4 isoform has a significantly different C-terminal composition than the prototypic NR1-1 isoform. Whereas the NR1-1 C terminus is composed of C0, C1, and C2 exon cassettes, the NR1-4 C terminus is composed of the C0 and C2' cassettes. In the present study, we address the importance of the NR1-4 C-terminal exon cassettes (C0C2') in subcellular localization in differentiated pheochromocytoma (PC12) cells, in organotypic cultures of dorsal root ganglia, and also in heterologous cells. NR1-4-green fluorescent protein chimeras were created with deletion of either C0, C2', or both cassettes to address their importance in subcellular distribution and cell surface expression of the NR1-4 subunit. These experiments demonstrate that the NR1-4 splice variant found predominantly in the spinal cord uses the C0 cassette, to a large degree, to organize the subcellular distribution of this receptor subunit. Although the role of the C2' subunit is less clear, it may be involved in subunit clustering. However, this clustering is not always as efficient as that attributed to C0 alone or to the natural combination of C0C2'. Finally, although an intact C-terminal domain is neither necessary for interaction with the NR2A subunit nor surface expression of the NR1-4 subunit, the C-terminal domain fragment alone blocks surface expression of native NR1-4, in a dominant negative fashion, when the two are coexpressed.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".