Auxiliary protein stoichiometry shapes permeation and gating properties of AMPARs
Bibliographic record
Abstract
AMPA receptors (AMPARs), a member of the ionotropic glutamate receptor (iGluRs) family, are responsible for mediating fast excitatory neurotransmission in the mammalian brain.Upon receiving information in the form of glutamate release from the presynaptic neuron, AMPARs rapidly open to briefly depolarize the postsynaptic neuron and then quickly deactivate, which effectively ensures precise and high-fidelity information transfer between neurons.Different neuronal cell types integrate this information differentially, and this process depend on the duration, amplitude and constituents of AMPAR-mediated currents.Hence, understanding the gating and permeation properties of AMPARs has long been a vehement area of research.Here, using a combination of in vitro recombinant electrophysiology and ex vivo slice electrophysiology technique, we investigated the modulatory effect of auxiliary proteins, specifically the TARPs and CNIHs, on AMPAR gating and permeation.Our work showed that AMPARs with different auxiliary protein stoichiometry exhibit distinct decay kinetics and equilibrium response upon external application of glutamate.Subsequently, we found that these unique gating profiles can be used to reliably deduce auxiliary protein stoichiometry of native AMPARs.Furthermore, we unexpectedly uncovered that certain auxiliary protein stoichiometry can dramatically augment Ca 2+ permeability of GluA2containing AMPARs, a class of AMPARs that has been dogmatically categorized as Ca 2+ impermeable.Taken together, these findings suggest that not only the type of auxiliary proteins, but also the stoichiometry of them have profound impact on gating and permeation properties of AMPARs, which points to an unappreciated regulatory mechanism of native AMPAR function. List of AbbreviationsAlzheimer's disease (AD) Amyotrophic lateral sclerosis (ALS) α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) Ca 2+ -impermeable AMPARs (CI-AMPARs) Ca 2+ -permeable AMPARs (CP-AMPARs) Central nervous system (CNS) CNIHs (cornichon auxiliary protein) Current-voltage (I-V) relationship Cyclothiazide (CTZ) C-terminal domain (CTD) Ionotropic glutamate receptors (iGluRs) Kainate receptors (KAR) Ligand binding domain (LBD) Medial nucleus of the trapezoid body (MNTB) Metabotropic glutamate receptors (mGluRs) N-methyl-d-aspartate (NMDA) N-terminal domain (ATD) Steady state to peak current (SS/PK) Transmembrane AMPAR Regulatory Protein (TARP) Transmembrane domain (TMD) Voltage gated sodium channels (Nav) Voltage-calcium calcium channels (Cav) Voltage-gated potassium channels (Kv)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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 | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".