구.추천논문
- 조회2,817
Abstract
Hyun-Ji Kim1†, Myong-Ho Jeong2†, Kyung-Ran Kim3,4†, Chang-Yun Jung2†, Seul-Yi Lee1, Hanna Kim1, Jewoo Koh1, Tuan Anh Vuong2, Seungmoon Jung5, Hyunwoo Yang5, Su-Kyung Park2, Dahee Choi2,6, Sung Hun Kim7, KyeongJin Kang8, Jong-Woo Sohn9, Joo Min Park10, Daejong Jeon11,12, Seung-Hoi Koo6, Won-Kyung Ho3,4, Jong-Sun Kang2*, Seong-Tae Kim2*, Hana Cho1*
1Department of Physiology, Samsung Biomedical Institute, Sungkyunkwan University School of Medicine, Suwon, Korea; 2Department of Molecular Cell Biology, Samsung Biomedical Institute, Sungkyunkwan University School of Medicine, Suwon, Korea; 3Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, Korea; 4Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, Korea; 5Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea; 6Division of Life Sciences, Korea University, Seoul, Korea; 7Department of Neurology, College of Medicine, Kangwon National University, Chuncheon, Korea; 8Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea; 9Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea; 10Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Korea; 11Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, Korea; 12Advanced Neural Technologies, Seoul, Republic of Korea
*For correspondence: Jong-Sun Kang; Seong-Tae Kim; Hana Cho
†These authors contributed equally to this work
Abstract
KCNQ channels are critical determinants of neuronal excitability, thus emerging as a novel target of anti-epileptic drugs. To date, the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors, Ca2+/CaM, and protein kinase C. Here we demonstrate that methylation of KCNQ by protein arginine methyltransferase 1 (Prmt1) positively regulates KCNQ channel activity, thereby preventing neuronal hyperexcitability. Prmt1+/- mice exhibit epileptic seizures. Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP2 binding, and Prmt1 depletion lowers PIP2 affinity of KCNQ2 channels and thereby the channel activities. Consistently, exogenous PIP2 addition to Prmt1+/- neurons restores KCNQ currents and neuronal excitability to the WT level. Collectively, we propose that Prmt1-dependent facilitation of KCNQ-PIP2 interaction underlies the positive regulation of KCNQ activity by arginine methylation, which may serve as a key target for prevention of neuronal hyperexcitability and seizures.
논문정보
- Research article
- 2016년 07월 (BRIC 등록일 2016-09-23)
- 국내 연구진
- 의약학 > 분자세포의학
- 구・추천논문
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