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UCH-L1 Inhibition Involved in CREB Dephosphorylation in Hippocampal Slices

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Abstract

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is abundantly expressed in the brain and is critical for the normal function of synapses. cAMP response element binding protein (CREB) is a transcription factor which initiates the expression of proteins that related to the regulation of synaptic plasticity and memory function. Studies have shown that UCH-L1 can influence the expression and activity of CREB, but the underlying mechanisms remain unclear. In this study, we used UCH-L1 inhibitor LDN to treat mice hippocampal slices and found that UCH-L1 inhibition caused the dephosphorylation of CREB at Ser133 site. Meanwhile, hyperphosphorylation of microtubule-associated protein tau; increased expression of synaptic protein components of PSD-95 and synapsin-1, and decreased activity of tyrosine kinase Fyn were observed after UCH-L1 inhibition. Moreover, all these alternations have an influence on the normal function of N-methyl-d-aspartate (NMDA) receptor NR2B subunit which is likely to result in the dephosphorylation of CREB. We also found that LDN treatment mediated protein kinase A (PKA) deactivation was involved in the dephosphorylation of CREB. Thus, our study introduces a novel possible mechanism for elaborating the effects of UCH-L1 inhibition on the CREB activity and the implicated signaling pathways.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 30700208, No. 30800329, and No. 31172102).

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Authors and Affiliations

  1. Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Number 152, Luoyu Road, Wuhan, 430079, China

    Min Xie, Shao-Hui Wang, Zhi-Min Lu, Ying Pan, Qi-Cai Chen & Xiao-Mei Liao

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  1. Min Xie
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  2. Shao-Hui Wang
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Correspondence to Xiao-Mei Liao.

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M. Xie and S.H. Wang contributed equally to this work.

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Xie, M., Wang, SH., Lu, ZM. et al. UCH-L1 Inhibition Involved in CREB Dephosphorylation in Hippocampal Slices. J Mol Neurosci 53, 59–68 (2014). https://doi.org/10.1007/s12031-013-0197-z

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  • DOI: https://doi.org/10.1007/s12031-013-0197-z

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