Regulatory effects of α-synuclein and PINK1 on Nurr1 activity

doi:10.3969/j.issn.1006-7795.2015.06.011

Abstract

Abstract: Objective To investigate if α-synuclein(α-syn) and PTEN induced putative kinase 1(PINK1) have an effect on nuclear receptor related 1(Nurr1) activity. Methods Two plasmids pAmCyan1-N1-α-syn(CFP-α-syn) and pZsYellow1-N1-Nurr1(YFP-Nurr1) were constructed to detect the interaction between α-syn and Nurr1 using fluorescence resonance energy transfer(FRET) technique. PINK1 gene was silenced with siRNA in MN9D cells followed by Nurr1 activity detection. Results After transfected with the above two plasmids, SK-N-SH cells were observed under the confocal microscopy. The fluorescence of CFP and YFP did not become weak with fusion of target protein. FRET phenomenon was observed and the FRET efficiency between CFP-α-syn and YFP-Nurr1 was about 21%, indicating that there was an interaction between α-syn and Nurr1. The results showed that Nurr1 activity was down-regulated when PINK1 gene was knocked-down for 24 h or 48 h, indicating that PINK1 had a regulatory effect on Nurr1 activity. Conclusion Therefore α-syn may be as a transcriptional repressor to inhibit Nurr1 activity by interacting with the latter. In contrary, PINK1 positively regulates Nurr1 activity. The coordination between PINK1 and α-syn may play an important role in DA homeostasis.

Key words: Parkinson's disease, α-synuclein, PTEN induced putative kinase 1, nuclear receptor related 1, transcriptional regulation

CLC Number:

R741

Lu Lingling, Shi Yuqing, Wei Yufei, Jia Huanzhen, Qiao Fangwei, Yang Hui. Regulatory effects of α-synuclein and PINK1 on Nurr1 activity[J]. Journal of Capital Medical University, 2015, 36(6): 895-901.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2015.06.011

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2015/V36/I6/895

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