Fu Wing-Yu, Fu Amy K Y, Lok Ka-Chun, Ip Fanny C F, Ip Nancy Y
Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Neuroreport. 2002 Feb 11;13(2):243-7. doi: 10.1097/00001756-200202110-00014.
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.
细胞周期蛋白依赖性激酶5（Cdk5）最初被鉴定为一种丝氨酸/苏氨酸激酶，随后被证明在中枢神经系统发育中起关键作用。我们最近报道了Cdk5在神经肌肉接头（NMJ）发育过程中神经调节蛋白信号通路中的新功能。在此，我们报道了神经损伤后大鼠骨骼肌中Cdk5和p35的调节情况。Northern印迹分析显示，神经去支配后肌肉中Cdk5和p35转录本上调。Cdk5和p35转录本调节的时间模式不同，表明这些基因转录的变化可能受不同机制调控。我们关于河豚毒素诱导肌肉中p35转录本能力的发现表明，电活动可调节p35表达。除了诱导mRNA表达外，神经去支配后肌肉中总的Cdk5和与p35相关的激酶活性显著增加。综上所述，我们的发现表明Cdk5和p35可能在神经损伤后的肌肉再生中发挥重要的生理作用。
