Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion protein to laminili γ1 chain
Bibliographic record
Abstract
The prion protein (PrP C ) is highly expressed in the nervous system, and its abnormal con‐former is associated with prion diseases. PrP C is anchored to cell membranes by glycosylphosphatidylinositol, and transmembrane proteins are likely required for PrP C ‐mediated intracellular signaling. Binding of laminin (Ln) to PrP C modulates neuronal plasticity and memory. We addressed signaling pathways triggered by PrP C ‐Ln interaction in order to identify transmembrane proteins involved in the transduction of PrP C ‐Ln signals. The Ln γl‐chain peptide, which contains the Ln binding site for PrP C , induced neuritogenesis through activation of phos‐pholipase C (PLC), Ca 2+ mobilization from intracellular stores, and protein kinase C and extracellular signalregulated kinase (ERK1/2) activation in primary cultures of neurons from wild‐type, but not PrP C ‐null mice. Phage display, coimmunoprecipitation, and colocalization experiments showed that group I metabotropic glutamate receptors (mGluRl/5) associate with PrP C . Expression of either mGluRl or mGluR5 in HEK293 cells reconstituted the signaling pathways mediated by PrP C ‐Ln γl peptide interaction. Specific inhibitors of these receptors impaired PrP C ‐Ln γl peptide‐induced signaling and neuri‐togenesis. These data show that group I mGluRs are involved in the transduction of cellular signals triggered by PrP C ‐Ln, and they support the notion that PrP C participates in the assembly of multiprotein complexes with physiological functions on neurons.—Beraldo, F. H., Arantes, C. P., Santos, T. G., Machado, C. F. , Roffe, M., Hajj, G. N., Lee, K. S., Magalhães, A. C., Caetano, F. A., Mancini, G. L., Lopes, M. H., Amãrico, T. A., Magdesian, M. H., Ferguson, S. S. G., Linden, R., Prado, M. A. M., Martins, V. R. Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion protein to laminin γl chain. FASEB J. 25, 265–279 (20ll). www.fasebj.org
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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) | 0.001 | 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 | 0.000 |
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".