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Overexpression of Tau Rescues Nogo-66-Induced Neurite Outgrowth Inhibition In Vitro

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Abstract

Nogo-66 plays a central role in the myelin-mediated inhibition of neurite outgrowth. Tau is a microtubule-associated protein involved in microtubule assembly and stabilization. It remains unverified whether tau interacts directly with growth factor receptors, or engages in cross-talk with regeneration inhibitors like Nogo-66. Here, we report that plasmid overexpression of tau significantly elevated the protein levels of total tau, phosphorylated tau, and microtubule-affinity regulating kinase (MARK). Nogo-66 transiently elevated the total tau protein level and persistently reduced the level of p-S262 tau (tau phosphorylated at serine 262), whereas it had little influence on the level of p-T205 tau (tau phosphorylated at threonine 205). Nogo-66 significantly decreased the protein level of MARK. Hymenialdisine, an inhibitor of MARK, significantly reduced the level of p-S262 tau. Overexpression of tau rescued the Nogo-66-induced inhibition of neurite outgrowth in neuroblastoma 2a (N2a) cells and primary cortical neurons. However, concomitant inhibition of MARK abolished the rescue of neurite outgrowth by tau in N2a cells. We conclude that dephosphorylation of tau at S262 is able to regulate Nogo-66 signaling, and that overexpression of tau can rescue the Nogo-66-induced inhibition of neurite outgrowth in vitro.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81371380 and 31171028).

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Authors and Affiliations

  1. Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Yu-Chao Zuo, Nan-Xiang Xiong, Yi-Zhi Huang, Peng Fu & Hong-Yang Zhao

  2. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Yu-Chao Zuo

  3. Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hong-Lian Li & Jian-Ying Shen

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  1. Yu-Chao Zuo
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  2. Hong-Lian Li
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  3. Nan-Xiang Xiong
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  5. Yi-Zhi Huang
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Correspondence to Nan-Xiang Xiong or Hong-Yang Zhao.

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Zuo, YC., Li, HL., Xiong, NX. et al. Overexpression of Tau Rescues Nogo-66-Induced Neurite Outgrowth Inhibition In Vitro . Neurosci. Bull. 32, 577–584 (2016). https://doi.org/10.1007/s12264-016-0068-z

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  • DOI: https://doi.org/10.1007/s12264-016-0068-z

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