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Regulation of 1, 4, 5-triphosphate receptor channel gating dynamics by mutant presenilin in Alzheimer’s disease cells

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Abstract

In neurons of patients with Alzheimer’s disease, the intracellular Ca2+ concentration is increased by its release from the endoplasmic reticulum via the inositol 1, 4, 5-triphosphate receptor (IP3R). In this paper, we discuss the IP3R gating dynamics in familial Alzheimer’s disease (FAD) cells induced with presenilin mutation PS1. By fitting the parameters of an IP3R channel model to experimental data of the open probability, the mean open time and the mean closed time of IP3R channels, in control cells and FAD mutant cells, we suggest that the interaction of presenilin mutation PS1 with IP3R channels leads the decrease in the unbinding rates of IP3 and the activating Ca2+ from IP3Rs. As a result, the increased affinities of IP3 and activating Ca2+ for IP3R channels induce the increase in the Ca2+ signal in FAD mutant cells. Specifically, the PS1 mutation decreases the IP3 dissociation rate of IP3R channels significantly in FAD mutant cells. Our results suggest possible novel targets for FAD therapeutic intervention.

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Acknowledgements

We acknowledge support from the National Natural Science Foundation of China (Grant Nos. 31370830 and 11675134), the 111 Project (Grant No. B16029), and the China Postdoctoral Science Foundation (Grant No. 2016M602071).

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Authors and Affiliations

  1. Department of Physics, Xiamen University, Xiamen, 361005, China

    Fang Wei, Meichun Cai, Yanping Liu & Jianwei Shuai

  2. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China

    Xiang Li & Jianwei Shuai

  3. Department of Physics and Astronomy and Quantitative Biology Institute, Ohio University, Athens, OH, 45701, USA

    Peter Jung

  4. Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen, 361005, China

    Jianwei Shuai

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  1. Fang Wei
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  2. Xiang Li
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  3. Meichun Cai
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  4. Yanping Liu
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Correspondence to Jianwei Shuai.

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Special Topic: Soft-Matter Physics and Complex Systems (Ed. Zhi-Gang Zheng).

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Wei, F., Li, X., Cai, M. et al. Regulation of 1, 4, 5-triphosphate receptor channel gating dynamics by mutant presenilin in Alzheimer’s disease cells. Front. Phys. 12, 128702 (2017). https://doi.org/10.1007/s11467-017-0670-1

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  • DOI: https://doi.org/10.1007/s11467-017-0670-1

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