A beta mediates Sigma receptor degradation via CaN/NFAT pathway

作者：Fang, Min; Zhang, Pei; Zhao, Yanxin; Jin, Aiping^*; Liu, Xueyuan^*

来源：American Journal of Translational Research, 2016, 8(8): 3471-3481.

• Alzheimer disease
• beta-amyloid
• sigma receptor
• calcineurin
• nuclear factor of activated T cells

Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the A beta induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of A beta on the Sigma receptor expression. Our results showed the increase in extracellular A beta had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression. Co-immunoprecipitation was employed to evaluate the interaction of Sigma receptor with other proteins. Results showed BIP could bind to Sigma receptor to affect the ubiquitination of Sigma receptor. Further investigation showed there was a NFAT binding site at the promoter of BIP. Then, Western blot assay was performed to detect NFAT expression. Results showed extracellular A beta affected the nuclear translocation of NFAT and the CaN activity of NFAT also increased with the accumulation of extracellular A beta. In this study, NFAT-BIP luciferase reporter gene system was constructed. Results showed NFAT was able to regulate the transcription of BIP. Thus, we speculate that extracellular A beta accumulation may activate CaN/NFAT signaling pathway to induce chaperone BIP expression, which results in Sigma receptor ubiquitination and its degradation.

• 出版日期2016
• 单位同济大学