MARK2 Rescues Nogo-66-Induced Inhibition of Neurite Outgrowth via Regulating Microtubule-Associated Proteins in Neurons In Vitro
MARK2 Rescues Nogo-66-Induced Inhibition of Neurite Outgrowth via Regulating Microtubule-Associated Proteins in Neurons In Vitro
复制标题
MARK2 通过调节体外神经元中的微管相关蛋白来挽救 Nogo-66 诱导的神经突生长抑制
DOI：
10.1007/s11064-016-2016-8
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Yu-Chao Zuo
中科院分区：
文献类型：
--
作者：
Nan-Xiang Xiong;Hong-Yang Zhao;Yu-Chao Zuo
成年哺乳动物中枢神经系统（CNS）中神经元在损伤后再生的能力是CNS髓磷脂中limited.by抑制剂。Nogo-66是最重要的髓鞘抑制剂，但Nogo-66抑制神经突起生长的机制仍不清楚。特别是，Nogo-66与微管亲和性调节激酶2（MARK 2）之间的关系尚未被研究。This.study neurons.in研究了MARK 2在Nogo-66抑制中的作用，以及MARK 2在体外神经突延伸中的功能。MARK 2和在Ser 212处磷酸化的MARK 2。在不同的Nogo-66暴露时间下评估Neuro 2a细胞中的p-Ser 212改变;通过MARK 2的过表达或干扰来确定MARK 2和微管相关蛋白（MAP）之间的关系。我们的研究报道Nogo-66抑制MARK 2的表达，但也减少MARK 2的Ser 212磷酸化，而MAP 1-B和tau的水平根据MARK 2的过表达或表达减少而变化。of.total此外，MARK 2增加酪氨酸化α-微管蛋白的比例，从而破坏微管蛋白的稳定性，最可能影响轴突生长。与这些结果一致，MARK 2的过表达促进神经突伸长，因此能够挽救Nogo-66对神经突生长的抑制作用。总之，细胞内PKB/MARK 2/MAPs/α-tubulin通路在体外培养的神经元突起伸长过程中起重要作用。这些结果表明MARK 2在克服Nogo-66诱导的神经元轴突生长抑制中的关键作用。MARK 2的药理学激活剂可适用于促进许多类型的CNS损伤后的成功轴突生长。
The ability of neurons in the adult mammalian central.nervous system (CNS) to regenerate after injury is limited.by inhibitors in CNS myelin. Nogo-66 is the most important.myelin inhibitor but the mechanisms of Nogo-66 inhibition.of neurite outgrowth remain poorly understood. Particularly,.the relationship between Nogo-66 and microtubule-affinity.regulating kinase 2 (MARK2) has not been examined. This.study investigated the role of MARK2 in Nogo-66 inhibition.and the function of MARK2 in neurite elongation in neurons.in vitro. MARK2 and phosphorylated MARK2 at Ser212.(p-Ser212) alterations in Neuro 2a cells were assessed at different.Nogo-66 exposure times; the relationships between.MARK2 and microtubule-associated proteins (MAPs) were.determined via the overexpression or interference of MARK2..Our study reports that Nogo-66 inhibited the expression of.total MARK2 but also reduced Ser212 phosphorylation of.MARK2, whereas levels of MAP1-b and tau varied depending.on MARK2 overexpression or reduced expression. Furthermore,.MARK2 increased the proportion of tyrosinated α-tubulin, thereby disrupting the stability of tubulin, most.likely affecting axonal growth. In line with these results,.overexpression of MARK2 promoted neurite elongation and.therefore is able to rescue the inhibitory effect of Nogo-66 on.neurite growth. In conclusion, the intracellular PKB/MARK2/.MAPs/α-tubulin pathway appears to be essential for neurite.elongation in neurons in vitro. These results suggest a critical.role for MARK2 in overcoming Nogo-66-induced inhibition.of axon outgrowth in neurons. Pharmacological activators of.MARK2 may be applicable to promote successful axonal outgrowth.following many types of CNS injuries.
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DOI：
10.1083/jcb.200902142
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Peris L;Wagenbach M;Lafanechère L;Brocard J;Moore AT;Kozielski F;Job D;Wordeman L;Andrieux A
通讯作者：
Andrieux A
影响因子：
5.3
作者：
Fournier, AE;Takizawa, BT;Strittmatter, SM
通讯作者：
Strittmatter, SM
影响因子：
4.8
作者：
T. Timm;Kiruthiga Balusamy;Xiao-yu Li;J. Biernat;E. Mandelkow;E. Mandelkow
通讯作者：
T. Timm;Kiruthiga Balusamy;Xiao-yu Li;J. Biernat;E. Mandelkow;E. Mandelkow
影响因子：
5.3
作者：
Yuta Yoshimura;T. Terabayashi;H. Miki
通讯作者：
Yuta Yoshimura;T. Terabayashi;H. Miki
影响因子：
5.7
作者：
Schwab ME;Strittmatter SM
通讯作者：
Strittmatter SM