Regulation of GluR1 by the A-Kinase Anchoring Protein 79 (AKAP79) Signaling Complex Shares Properties with Long-Term Depression
Bibliographic record
Abstract
Second messengers regulate synaptic plasticity by influencing the balance between kinase and phosphatase activity. One target of this balance is the phosphorylation state of the AMPA receptor glutamate receptor 1 (GluR1) subunit. Hippocampal long-term depression (LTD) is a calcium-dependent downregulation of synaptic AMPA receptor currents associated with dephosphorylation of Ser845, a cAMP-dependent protein kinase (PKA) site on GluR1. Recruitment of kinases and phosphatases to the AMPA receptor might enable modulation of AMPA receptor function. The neuronal A-kinase anchoring protein AKAP79/150 interacts with PKA and the calcium-dependent protein phosphatase PP2B and is linked to the AMPA receptor GluR1 subunit by synapse-associated protein 97 (SAP97), a membrane-associated guanylate kinase family protein. Here we demonstrate that AKAP79 not only promotes basal phosphorylation of Ser845 but also confers a calcium- and PP2B-mediated downregulation to GluR1 receptor currents. This AKAP79-dependent downregulation is contingent on the local presence of PKA, Ser845 of GluR1, and a PDZ (postsynaptic density 95/Discs large/zona occludens 1)-domain interaction between GluR1 and SAP97, all of which support basal phosphorylation of the receptor. These findings suggest that the AKAP79 signaling complex is sufficient to couple intracellular calcium levels to the PKA phosphorylation state of GluR1. Thus, the integration of intracellular signals relevant for LTD may be transduced to GluR1 by the AKAP79 signaling complex.
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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) | 0.001 | 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".