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Induction of Cdk5 activity in rat skeletal muscle after nerve injury
Wing-Yu Fu1, Amy K Y Fu, Ka-Chun Lok
1Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Abstract:
Cyclin-dependent kinase 5 (Cdk5) was originally identified as a serine/threonine kinase and subsequently demonstrated to play a critical role in the development of CNS. We recently reported the novel function of Cdk5 in the neuregulin signaling pathway during the development of neuromuscular junction (NMJ). Here, we report the regulation of Cdk5 and p35 in rat skeletal muscle after nerve injury. Northern blot analysis revealed that Cdk5 and p35 transcripts were up-regulated in muscle after nerve denervation. The temporal profiles for the regulation of Cdk5 and p35 transcripts were different, suggesting that these changes in gene transcription might be regulated by different mechanism. Our finding on the ability of tetrodotoxin to induce p35 transcript in muscle suggested that electrical activity could regulate p35 expression. In addition to the induction of mRNA expression, the total Cdk5 and p35-associated kinase activity in muscle increased prominently after nerve denervation. Taken together, our findings suggest that Cdk5 and p35 may play important physiological roles in muscle regeneration following nerve injury.
Insights
Cyclin-dependent kinase 5 (Cdk5) and its activator p35 are upregulated in rat skeletal muscle after nerve injury. These findings suggest Cdk5 and p35 play roles in muscle regeneration following nerve damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Muscle Physiology
Background:
- Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase crucial for central nervous system (CNS) development.
- Cdk5 has a recently identified role in the neuregulin signaling pathway during neuromuscular junction (NMJ) development.
Purpose of the Study:
- To investigate the regulation of Cdk5 and its activator p35 in rat skeletal muscle following nerve injury.
- To explore the potential physiological roles of Cdk5 and p35 in muscle regeneration.
Main Methods:
- Northern blot analysis to assess Cdk5 and p35 transcript levels after nerve denervation.
- Administration of tetrodotoxin to evaluate the role of electrical activity on p35 expression.
- Measurement of Cdk5 and p35-associated kinase activity in muscle tissue.
Main Results:
- Cdk5 and p35 transcripts were significantly upregulated in skeletal muscle after nerve denervation.
- The temporal patterns of Cdk5 and p35 transcript regulation differed, indicating distinct regulatory mechanisms.
- Electrical activity, modulated by tetrodotoxin, influenced p35 transcript expression.
- Both total Cdk5 and p35 protein levels and their associated kinase activity increased notably post-denervation.
Conclusions:
- Cdk5 and p35 expression and activity are modulated in skeletal muscle following nerve injury.
- These findings suggest that Cdk5 and p35 are involved in the physiological processes of muscle regeneration after nerve damage.