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Axonal Mechanotransduction Drives Cytoskeletal Responses to Physiological Mechanical Forces
Grace L Swaim1,2,3, Oliver V Glomb1,3, Yi Xie1
1Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510.
Biorxiv : the Preprint Server for Biology
|February 24, 2025
Summary
External forces shape axon structure and integrity. This study reveals how muscle contractions drive axonal cytoskeletal responses via mechanotransduction, essential for preventing axon breakage.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Axons are subjected to mechanical forces from animal movement.
- The role of these forces in non-mechanosensory neurons is not well understood.
- Axonal integrity is crucial for nervous system function.
Purpose of the Study:
- To investigate the axonal cytoskeletal response to physiological forces.
- To identify the signaling pathways involved in this response.
- To understand how mechanical forces impact axonal integrity.
Main Methods:
- Live imaging of microtubules in *C. elegans* motor neurons.
- Cell-specific chemogenetics and targeted protein degradation.
- Genetic manipulation of spectrin-based cytoskeleton and mechanotransduction pathways.
Main Results:
- Muscle contractions drive local microtubule oscillations in axons.
- These oscillations depend on Talin, RhoA, and axonal actomyosin.
- Disrupting the spectrin cytoskeleton leads to cytoskeletal defects and axon degeneration.
- Mechanotransduction signaling and force buffering are critical for axonal integrity.
Conclusions:
- Identified a novel axonal cytoskeletal response to physiological forces.
- Demonstrated the importance of force-buffering and mechanotransduction for axonal integrity.
- Uncovered mechanisms linking external forces to cytoskeletal dynamics and axon health.
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