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Following OGD/R, Annexin 1 Nuclear Translocation and Subsequent Induction of Apoptosis in Neurons Are Assisted by Myosin IIA in a TRPM7 Kinase-Dependent Manner

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Abstract

Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a bifunctional channel protein that contains an α-kinase domain at its C-terminal. Previous studies have indicated that oxygen-glucose deprivation/reoxygenation (OGD/R) induces neuronal apoptosis via TRPM7. Annexin 1 and myosin IIA have been identified as TRPM7 kinase substrates; however, the role of annexin 1 in OGD/R-induced neuron apoptosis remains unclear. Here, we report that OGD/R induces nuclear translocation of annexin 1 in primary cultured neurons. Interestingly, ablation of the TRPM7 kinase or a point mutation in Ser5 interferes with TRPM7 kinase-annexin 1 binding, decreasing annexin 1 nuclear translocation, and thereby reducing neuronal apoptosis. Furthermore, mutation of Arg205, which intercepts annexin 1-formyl peptide receptor binding, also decreased annexin 1 nuclear translocation. Coimmunoprecipitation indicated that annexin 1 is moved as cargo through the cytoplasm by myosin IIA. However, inhibiting myosin IIA can decrease annexin 1 nuclear translocation. Moreover, blocking myosin IIA function by antagonist injection into the lateral ventricle was found to improve learning and memory in rats after middle cerebral artery occlusion and could also improve cell viability after OGD/R. Last, we determined that the annexin 1-myosin IIA complex is recognized and translocated by the importin α/β heterodimer. Therefore, TRPM7 kinase modulates OGD/R-induced neuronal apoptosis via annexin 1 carried by myosin IIA, while nuclear formyl peptide receptor (FPR)-annexin 1 binding and importin β are involved in nuclear translocation.

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Acknowledgments

The current studies were supported by funding from the National Natural Science Foundation of China, program number 31171029. We appreciate the gift of the expression vectors (pcDNA5/FRT/TO) containing amino terminal hemagglutinin (HA)-tagged murine TRPM7 or TRPM7ΔKin (made by changing the TCG codon encoding serine 1501 into a stop codon) from Loren W. Runnels, UMDNJ-Robert Wood Johnson Medical School, USA. Finally, we would like to thank BGI-Shenzhen, especially Junhua Rao and Wei Chen, for their efficient and professional work on the ChIP-Seq analysis.

Conflict of Interest

The authors declare that they have no conflict of interest.

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  1. Department of Neurobiology and Key Laboratory of Neurological Disease of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People’s Republic of China

    Yin Zhao, Jing Wang, Hui Jiang, Zhumei Yu, Xing Li & Jing Shi

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  1. Yin Zhao
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  3. Hui Jiang
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Correspondence to Jing Shi.

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Zhao, Y., Wang, J., Jiang, H. et al. Following OGD/R, Annexin 1 Nuclear Translocation and Subsequent Induction of Apoptosis in Neurons Are Assisted by Myosin IIA in a TRPM7 Kinase-Dependent Manner. Mol Neurobiol 51, 729–742 (2015). https://doi.org/10.1007/s12035-014-8781-y

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  • DOI: https://doi.org/10.1007/s12035-014-8781-y

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