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The expression of receptor tyrosine phosphatases is responsive to sciatic nerve crush
1Department of Human Anatomy, University of Oxford, Oxford, OX1 3QX, UK.
Abstract:
Given the importance of phosphotyrosine signaling in growth cone dynamics, we have examined the embryonic and adult expression of receptor-like protein tyrosine phosphatases in sensory neurons and studied their responsiveness to nerve lesions in young adult animals. The phosphatases LAR, PTPsigma, and PTPalpha are expressed in most neurons of E14 and E18 rat embryo dorsal root ganglia, while BEM-1 is expressed in a more restricted subset of these neurons. These phosphatases continue to be expressed in young adult animals, suggesting that they have roles in mature as well as in developing dorsal root ganglia neurons. After an experimental sciatic nerve crush, the expression of the phosphatase genes was significantly and differentially altered in these neurons. PTPsigma mRNA was increased by 50% after 3 days, while LAR and PTPalpha expression dropped by 50 and 20%, respectively. BEM-1 mRNA levels were unaltered. These data show that mRNA levels of specific tyrosine phosphatase genes are highly responsive to nerve damage and may be reset to a new and potentially optimal pattern of expression more conducive for nerve regeneration. We propose that tyrosine phosphatases are not only involved in primary axonogenesis but can also now be implicated in the molecular control of adult nerve repair.
Insights
Receptor-like protein tyrosine phosphatases are present in sensory neurons from embryo to adulthood. Nerve injury alters their expression, suggesting a role in adult nerve repair and regeneration.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Phosphotyrosine signaling is crucial for growth cone dynamics.
- Receptor-like protein tyrosine phosphatases (RPTPs) are key regulators of cellular signaling.
- Understanding RPTPs in sensory neurons is vital for nerve repair research.
Purpose of the Study:
- To investigate the expression of RPTPs (LAR, PTPsigma, PTPalpha, BEM-1) in developing and adult sensory neurons.
- To determine the responsiveness of these RPTPs to sciatic nerve injury in adult rats.
Main Methods:
- Quantitative analysis of RPTP gene expression in dorsal root ganglia (DRG) neurons.
- Sciatic nerve crush model in young adult rats.
- Measurement of mRNA levels of specific RPTPs post-injury.
Main Results:
- LAR, PTPsigma, and PTPalpha are broadly expressed in embryonic and adult DRG neurons.
- Sciatic nerve crush significantly altered RPTP gene expression: PTPsigma mRNA increased, LAR and PTPalpha mRNA decreased.
- BEM-1 mRNA levels remained unchanged after nerve injury.
Conclusions:
- Specific tyrosine phosphatase gene expression is highly sensitive to nerve damage.
- RPTPs may play a role in adult nerve regeneration and repair.
- These findings implicate RPTPs in both primary axonogenesis and adult nerve repair mechanisms.