ID: h-d8e13922ed22
Hypothesis
MAP6-CRMPS cooperative phosphorylation by GSK3β
MAP6 and CRMP2 may be simultaneously phosphorylated by GSK3β at shared or interacting sites, creating a coordinated phosphorylation code that regulates microtubule dynamics in response to guidance cues.
EvidenceStrong (65%)📖 6 cit🗣 1 debates✓ 6 support✗ 2 oppose
⚠ Orphaned Senate Quality Gates →
🧪 Overview
MAP6 and CRMP2 may be simultaneously phosphorylated by GSK3β at shared or interacting sites, creating a coordinated phosphorylation code that regulates microtubule dynamics in response to guidance cues
Prediction: Simultaneous disruption of MAP6 and CRMP2 phosphorylation sites would produce more severe axon guidance defects than single knockouts, and neuronal activity-dependent phosphorylation events would show correlated changes in both proteins
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["MAPT/Tau Occupancy<br/>Dynamic Microtubule Binding"]
B["MAP6 Occupancy<br/>Cold-Stable Domain Support"]
C["Shared Microtubule Lattice<br/>Domain Allocation Competition"]
D["GSK3B/CRMP2 Cue Integration<br/>Plasticity Signaling"]
E["Axonal Remodeling Balance<br/>Stable vs Labile Segments"]
F["Transport and Branching<br/>Adaptive Circuit Plasticity"]
G["Tau-MAP6 Imbalance<br/>Rigid or Unstable Cytoskeleton"]
A --> C
B --> C
C --> D
D --> E
E --> F
G -.->|"disrupts"| C
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#1b5e20,stroke:#81c784,color:#81c784
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix6 supports0 contradicts
Supports
MAP6 and CRMP2 may be simultaneously phosphorylated by GSK3β at shared or interacting sites, creating a coordinated phosphorylation code that regulates microtubule dynamics in response to guidance cues
Supports
Druggability of CRMP2 for Neurodegenerative Diseases.
Supports
Dysregulation of CRMP2 Post-Translational Modifications Drive Its Pathological Functions.
Supports
Spastin Interacts with CRMP2 to Regulate Neurite Outgrowth by Controlling Microtubule Dynamics through Phosphorylation Modifications.
Supports
Antagonistic roles of tau and MAP6 in regulating neuronal development.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — MAP6
No curated PDB or AlphaFold mapping for MAP6 yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for MAP6/CRMP2 from GTEx v10.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for MAP6.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▼ 0.3%
Volatility
High
0.1165
Events (7d)
2
Price History
▼5.4%💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF primary rodent hippocampal neurons are treated with a selective GSK3β inhibitor (CHIR99021, 10 μM) for 24 hours, THEN phospho-S9-GSK3β inhibition will produce a coordinated decrease in p-CRMP2(S522 | Simultaneous reduction of p-MAP6(S236) and p-CRMP2(S522) by >40% in western blot analysis, with correlated temporal dynamics between the two phosphoproteins | — no observation — | pending | 0.65 |
| IF CRISPR-Cas9 is used to generate MAP6 S236A;CRMP2 S522A double knock-in mice (simultaneous alanine substitution at both phosphorylation sites), THEN cortical neurons from these mice will display exa | Double mutants show synergistic increase in growth cone collapse percentage and decrease in microtubule polymerization rate relative to single mutants and wild- | — no observation — | pending | 0.55 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF primary rodent hippocampal neurons are treated with a selective GSK3β inhibitor (CHIR99021, 10 μM) for 24 hours, THEN phospho-S9-GSK3β inhibition will produce a coordinated decrease in p-CRMP2(S522) and p-MAP6(S236) levels with a correlation coefficient >0.7 across neuronal preparations, within 4
Predicted outcome: Simultaneous reduction of p-MAP6(S236) and p-CRMP2(S522) by >40% in western blot analysis, with correlated temporal dynamics between the two phosphopr
Falsification: GSK3β inhibition affects phosphorylation of only one protein (MAP6 or CRMP2) while leaving the other unchanged; or phosphorylation changes are anti-correlated (r < 0.0); or neither protein's phosphory
pendingconf 55%
IF CRISPR-Cas9 is used to generate MAP6 S236A;CRMP2 S522A double knock-in mice (simultaneous alanine substitution at both phosphorylation sites), THEN cortical neurons from these mice will display exaggerated growth cone collapse (>60% collapse rate) and microtubule plus-end instability (>30% reduct
Predicted outcome: Double mutants show synergistic increase in growth cone collapse percentage and decrease in microtubule polymerization rate relative to single mutants
Falsification: Double mutant phenotype is statistically indistinguishable from wild-type (no facilitation); or single mutant phenotypes are equal to or greater than double mutant (no cooperative requirement); or mic
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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