Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression

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Title
Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression
Author(s)
Hyun-Ji Kim; Myong-Ho Jeong; Kyung-Ran Kim; Chang-Yun Jung; Seul-Yi Lee; Hanna Kim; Jewoo Koh; Tuan Anh Vuong; Seungmoon Jung; Hyunwoo Yang; Su-Kyung Park; Dahee Choi; Sung Hun Kim; KyeongJin Kang; Jong-Woo Sohn; Joo Min Park; Daejong Jeon; Seung-Hoi Koo; Won-Kyung Ho; Jong-Sun Kang; Seong-Tae Kim; Hana Cho
Publication Date
2016-07
Journal
ELIFE, v.5, no., pp.e17159 -
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
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. © Kim et al
URI
https://pr.ibs.re.kr/handle/8788114/2997
ISSN
2050-084X
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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