MAP6 may scaffold signaling complexes at synapses in an activity-dependent manner, linking NMDA receptor activation to cytoskeletal remodeling via its multiple functional domains
Prediction: MAP6 will physically associate with synaptic signaling proteins in a phosphorylation-dependent manner, and LTP-inducing stimulation will recruit MAP6 to dendritic spines
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 neuronal activity is selectively increased via chemogenetic activation of excitatory neurons in cultured hippocampal networks, THEN MAP6 protein will show a significant increase in synaptic spine l | Increased MAP6 accumulation at dendritic spines as measured by live-cell imaging of MAP6-GFP expressing neurons | — no observation — | pending | 0.65 |
| IF MAP6 phosphorylation-deficient knockin mice (S→A mutations at predicted activity-regulated sites) are subjected to theta-burst LTP induction, THEN the maintenance phase of LTP (60-120 min post-indu | Reduced LTP maintenance magnitude (≤150% of baseline) at Schaffer collateral-CA1 synapses in knockin vs wild-type mice | — no observation — | pending | 0.58 |