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Updated: Sep 15, 2025
10:38
Author Spotlight: Understanding the Impact of Pathological Proteins on Axonal Transport in Neurodegenerative Diseases
Published on: December 22, 2023
668
GSK-3β coordinates axonal microtubule organisation through Shot and Tau
Biorxiv : the Preprint Server for Biology
|July 14, 2025
Summary
Glycogen Synthase Kinase 3β (GSK-3β) is crucial for neuronal health. Dysregulated GSK-3β disrupts microtubule organization, leading to neurodegeneration, offering new therapeutic insights.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Glycogen Synthase Kinase 3β (GSK-3β) is vital for neuronal development and maintenance.
- Hyperactive GSK-3β is implicated in neurodevelopmental and neurodegenerative diseases.
- GSK-3β regulates the neuronal cytoskeleton via phosphorylation of microtubule-binding proteins.
Purpose of the Study:
- To investigate the role of GSK-3β kinase activity in maintaining axonal microtubule organization.
- To identify GSK-3β targets involved in microtubule bundling.
- To elucidate the mechanism by which GSK-3β misregulation leads to neurodegeneration.
Main Methods:
- Studied GSK-3β regulation of microtubule bundles in *Drosophila* and rat axons.
- Analyzed the effects of GSK-3β up- or down-regulation on axonal structure.
- Identified Shot and Tau as key GSK-3β targets and examined their interaction with microtubules and Eb1.
Main Results:
- Tight regulation of GSK-3β activity is essential for parallel microtubule bundle maintenance in axons.
- Altered GSK-3β levels caused pathological axonal swellings with disorganized microtubules.
- GSK-3β regulates the association of Shot and Tau with microtubules and Eb1, impacting microtubule organization.
Conclusions:
- GSK-3β misregulation disrupts microtubule organization through its targets Shot and Tau.
- Loss of Eb1-Shot-mediated microtubule guidance contributes to neurodegeneration.
- Microtubule disorganization offers a novel explanation for GSK-3β-linked neurodegeneration and challenges of clinical inhibition.
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