Mechanosensitive TRPC1 Channels Promote Calpain Proteolysis of Talin to Regulate Spinal Axon Outgrowth

The Journal of Neuroscience, 2013 · DOI: 10.1523/JNEUROSCI.2142-12.2013 · Published: January 2, 2013

Simple Explanation

This study investigates how mechanical cues influence axon guidance in developing spinal neurons. It focuses on Transient Receptor Potential Canonical 1 (TRPC1) channels, which are sensitive to mechanical stimuli. The researchers found that TRPC1 channels assemble on neuronal growth cones and regulate axon extension and direction, specifically on rigid surfaces. The influx of calcium ions through these channels activates calpain, a protease. Calpain then cleaves talin, an integrin adaptor protein, which reduces axon outgrowth. The study also shows that asymmetric inhibition of TRPC1 can induce growth cone turning, suggesting its role in axon guidance decisions.

Study Duration

Not specified

Participants

Xenopus spinal neurons

Evidence Level

In vitro experiments

Key Findings

1
TRPC1 subunits assemble mechanosensitive channels on Xenopus neuronal growth cones, regulating axon outgrowth on rigid substrates.
2
Calcium influx through MS TRPC1 activates calpain, which cleaves talin to reduce Src-dependent axon outgrowth.
3
Asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning, indicating its role in axon guidance.

Research Summary

This study identifies TRPC1 subunit-containing channels as mechanosensitive (MS) channels on spinal neuron growth cones. Increasing or decreasing MS channel activity alters axon outgrowth by influencing filopodial Ca2+ transients on rigid substrata. The protease calpain is activated by Ca2+ influx through MS channels and reduces axon outgrowth through proteolytic cleavage of the integrin-binding protein talin. Asymmetric MS channel activity induces growth cone turning, suggesting that environmental elastic properties influence axon outgrowth and guidance during development and regeneration.

Practical Implications

Axon Guidance Mechanisms

Mechanical cues, mediated by TRPC1 channels and calpain activation, play a critical role in guiding axon growth and direction during neural development.

Therapeutic Potential

Targeting TRPC1 channels or calpain activity could offer new therapeutic strategies for promoting axon regeneration after spinal cord injury or other neurological disorders.

Cellular Microenvironment

The rigidity of the cellular microenvironment significantly influences axon behavior, highlighting the importance of considering mechanical properties in studies of neural development and regeneration.

Study Limitations

1
The study focuses on Xenopus spinal neurons, and the findings may not be directly applicable to other species or neuronal types.
2
The specific mechanisms by which mechanical forces activate TRPC1 channels remain unclear.
3
The study primarily uses in vitro experiments, and further in vivo studies are needed to confirm the role of TRPC1 and calpain in axon guidance.

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