MAP6 stability activity may suppress adjacent tau lability activity through direct physical interaction or by altering tubulin post-translational modifications
Prediction: MAP6 overexpression will extend stability into adjacent tau-rich regions; MAP6 knockout will extend lability into MAP6-rich regions
Curated pathway from expert analysis
flowchart TD
A["MAP6 Occupancy on Microtubules<br/>Cold-Stable Cytoskeletal Support"]
B["Tau/MAPT Lattice Competition<br/>Dynamic Binding Balance"]
C["Synaptic Remodeling Signals<br/>NMDA-Linked Cytoskeletal Plasticity"]
D["Axonal Transport and Branching<br/>Circuit Adaptation"]
E["MAP6-Tau Imbalance<br/>Rigid or Unstable Cytoskeleton"]
A --> B
B --> C
C --> D
E -.->|"disrupts"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#1b5e20,stroke:#81c784,color:#81c784
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for MAP6 yet. Search RCSB →
Median TPM across 13 brain regions for MAP6 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.
No resource usage or linked notebooks recorded for this hypothesis yet.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF MAP6 is genetically ablated in iPSC-derived cortical neurons using CRISPR/Cas9, THEN the proportion of neurons exhibiting cytosolic mislocalization of tau (co-localization ratio <0.3 with axonal ma | At least 40% of MAP6-knockout neurons showing tau mislocalization vs. <20% in controls, quantified by high-content immunofluorescence imaging and automated neur | — no observation — | pending | 0.38 |
| IF MAP6 is overexpressed 2-fold in primary mouse cortical neurons via AAV2/9 transduction, THEN the ratio of pS396-tau to total tau in detergent-soluble fractions will decrease by at least 30% compare | Decreased tau phosphorylation at Ser396 by ≥30% in MAP6-overexpressing neurons as measured by quantitative western blot (normalized to β3-tubulin loading contro | — no observation — | pending | 0.45 |