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
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Curated Mechanism Pathway
Curated pathway diagram from expert analysis
flowchart TD
A["MAP6 Occupancy on Microtubules Cold-Stable Cytoskeletal Support"]
B["Tau/MAPT Lattice Competition Dynamic Binding Balance"]
C["Synaptic Remodeling Signals NMDA-Linked Cytoskeletal Plasticity"]
D["Axonal Transport and Branching Circuit Adaptation"]
E["MAP6-Tau Imbalance 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:#ef9a9a
Median TPM across 13 brain regions for MAP6 from GTEx v10.
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8 citations7 with PMID7 mediumValidation: 0%6 supporting / 2 opposing
✓For(6)
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Evidence Matrix — sortable by strength/year, click Abstract to expand
MAP6 may scaffold signaling complexes at synapses …
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Legacy Card View — expandable citation cards
✓ Supporting Evidence
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MAP6 may scaffold signaling complexes at synapses in an activity-dependent manner, linking NMDA receptor activ…▼
MAP6 may scaffold signaling complexes at synapses in an activity-dependent manner, linking NMDA receptor activation to cytoskeletal remodeling via its multiple functional domains
Tau/MAP6 antagonism is shown in neuronal development models, but this does not establish that the same balance…MEDIUM▼
Tau/MAP6 antagonism is shown in neuronal development models, but this does not establish that the same balance drives adult neurodegeneration progression or treatment response.
A microtubule-stabilizing peptide strategy failed to show clinical benefit in progressive supranuclear palsy, …MEDIUM▼
A microtubule-stabilizing peptide strategy failed to show clinical benefit in progressive supranuclear palsy, cautioning against simple cytoskeletal-stabilization translation in tauopathy.
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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 localization (≥40% increase in spine/cytoplasm ratio) within 60 minutes post-stimulation.
pendingconf: 0.65
Expected outcome: Increased MAP6 accumulation at dendritic spines as measured by live-cell imaging of MAP6-GFP expressing neurons
Falsified by: MAP6 spine/cytoplasm ratio changes by <20% or shows no change despite robust neuronal activity increase (c-Fos upregulation ≥3-fold confirms activation)
Method: Dissociated hippocampal neuron cultures from E18 rats, transfected with MAP6-GFP and hM3Dq-mCherry, treated with CNO (10μM) for activity induction, live confocal microscopy time-lapse imaging at 15-min intervals for 90 min
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-induction) will show significantly reduced potentiation compared to wild-type littermates.
pendingconf: 0.58
Expected outcome: Reduced LTP maintenance magnitude (≤150% of baseline) at Schaffer collateral-CA1 synapses in knockin vs wild-type mice
Falsified by: LTP maintenance in knockin mice remains within 10% of wild-type magnitude (both ≥160% baseline), indicating MAP6 phosphorylation is not required for LTP
Method: Acute hippocampal brain slices from 8-12 week old male MAP6 phospho-mutant mice and WT controls, field recordings at CA1 stratum radiatum, theta-burst stimulation (4 trains of 100Hz/1s), LTP measured 60-180 min post-induction
Knowledge Subgraph (0 edges)
No knowledge graph edges recorded
Predicted Protein Structure
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MAP6 — AlphaFold Prediction Q96JE9Click to expand 3D viewer
AI-predicted structure from AlphaFold | Powered by Mol* | Rotate: click+drag | Zoom: scroll | Reset: right-click