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Protein arginine methyltransferase 7 modulates neuronal excitability by interacting with NaV1.9.

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单位： [1]College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, China [2]Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China, [3]Department of Anesthesiology, Tongji Hospital of HUST, Wuhan, China, [4]Department of Medical Genetics, the Second Xiangya Hospital, Central South University, Changsha, China

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关键词： Na(v)1 9 PRMT7 Dorsal root ganglia Neuronal excitability DS-437

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Human NaV1.9 (hNaV1.9), encoded by SCN11A, is preferentially expressed in nociceptors, and its mutations have been linked to pain disorders. NaV1.9 could be a promising drug target for pain relief. However, the modulation of NaV1.9 activity has remained elusive. Here, we identified a new candidate NaV1.9-interacting partner, protein arginine methyltransferase 7 (PRMT7). Whole-cell voltage-clamp recordings showed that coelectroporation of human SCN11A and PRMT7 in dorsal root ganglion (DRG) neurons of Scn11a-/- mice increased the hNaV1.9 current density. By contrast, a PRMT7 inhibitor (DS-437) reduced mNaV1.9 currents in Scn11a+/+ mice. Using the reporter molecule CD4, we observed an increased distribution of hLoop1 on the cell surface of PRMT7-overexpressing HKE293T cells. Furthermore, we found that PRMT7 mainly binds to residues 563 to 566 within the first intracellular loop of hNaV1.9 (hLoop1) and methylates hLoop1 at arginine residue 519. Moreover, overexpression of PRMT7 increased the number of action potential fired in DRG neurons of Scn11a+/+ mice but not Scn11a-/- mice. However, DS-437 significantly inhibited the action potential frequency of DRG neurons and relieved pain hypersensitivity in Scn11aA796G/A796G mice. In summary, our observations revealed that PRMT7 modulates neuronal excitability by regulating NaV1.9 currents, which may provide a potential method for pain treatment.Copyright © 2021 International Association for the Study of Pain.

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出版当年[2021]版：

大类 | 1 区

医学

小类 | 2 区麻醉学 2 区临床神经病学 2 区神经科学

最新[2025]版：

大类 | 1 区

医学

小类 | 2 区麻醉学 2 区临床神经病学 2 区神经科学

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出版当年[2020]版：

Q1 CLINICAL NEUROLOGY Q1 ANESTHESIOLOGY Q1 NEUROSCIENCES

最新[2023]版：

Q1 ANESTHESIOLOGY Q1 CLINICAL NEUROLOGY Q1 NEUROSCIENCES

影响因子： 5.9 最新[2023版] 7.1 最新五年平均 6.961 出版当年[2020版] 7.704 出版当年五年平均 5.483 出版前一年[2019版] 7.926 出版后一年[2021版]

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第一作者单位： [1]College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, China

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通讯机构： [2]Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China, [*1]Institutes of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China

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