Calcineurin Inhibitor Protein (CAIN) Attenuates Group I Metabotropic Glutamate Receptor Endocytosis and Signaling
Bibliographic record
Abstract
Group I metabotropic glutamate receptors (mGluRs) are coupled via phospholipase Cbeta to the hydrolysis of phosphoinositides and function to modulate neuronal excitability and synaptic transmission at glutamatergic synapses. The desensitization of Group I mGluR signaling is thought to be mediated primarily via second messenger-dependent protein kinases and G protein-coupled receptor kinases. We show here that both mGluR1 and mGluR5 interact with the calcineurin inhibitor protein (CAIN). CAIN is co-immunoprecipitated in a complex with Group I mGluRs from both HEK 293 cells and mouse cortical brain lysates. Purified CAIN and its C-terminal domain specifically interact with glutathione S-transferase fusion proteins corresponding to the second intracellular loop and the distal C-terminal tail domains of mGluR1. The interaction of CAIN with mGluR1 could also be blocked using a Tat-tagged peptide corresponding to the mGluR1 second intracellular loop domain. Overexpression of full-length CAIN attenuates the agonist-stimulated endocytosis of both mGluR1a and mGluR5a in HEK 293 cells, but expression of the CAIN C-terminal domain does not alter mGluR5a internalization. In contrast, overexpression of either full-length CAIN or the CAIN C-terminal domain impairs agonist-stimulated inositol phosphate formation in HEK 293 cells expressing mGluR1a. This CAIN-mediated antagonism of mGluR1a signaling appears to involve the disruption of receptor-Galpha(q/11) complexes. Taken together, these observations suggest that the association of CAIN with intracellular domains involved in mGluR/G protein coupling provides an additional mechanism by which Group I mGluR endocytosis and signaling are regulated.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".