Protein Arginine Methylation Facilitates KCNQ Channel-PIP2 Interaction Leading to Seizure Suppression

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dc.contributor.authorKim, Hyun-Jiko
dc.contributor.authorJeong, Myong-Hoko
dc.contributor.authorKim, Kyung-Ranko
dc.contributor.authorJung, Chang-Yunko
dc.contributor.authorLee, Seul-Yiko
dc.contributor.authorKim, Hannako
dc.contributor.authorKoh, Jewooko
dc.contributor.authorVuong, Tuan Anhko
dc.contributor.authorJung, Seungmoonko
dc.contributor.authorYang, Hyunwooko
dc.contributor.authorPark, Su-Kyungko
dc.contributor.authorChoi, Daheeko
dc.contributor.authorKim, Sung Hunko
dc.contributor.authorKang, KyeongJinko
dc.contributor.authorSohn, Jong-Wooko
dc.contributor.authorPark, Joo Minko
dc.contributor.authorJeon, Daejongko
dc.contributor.authorKoo, Seung-Hoiko
dc.contributor.authorHo, Won-Kyungko
dc.contributor.authorKang, Jong-Sunko
dc.contributor.authorKim, Seong-Taeko
dc.contributor.authorCho, Hanako
dc.date.accessioned2016-09-08T00:49:47Z-
dc.date.available2016-09-08T00:49:47Z-
dc.date.created2016-09-05-
dc.date.created2016-09-05-
dc.date.created2016-09-05-
dc.date.issued2016-07-
dc.identifier.citationeLife, v.5-
dc.identifier.issn2050-084X-
dc.identifier.urihttp://hdl.handle.net/10203/212918-
dc.description.abstractKCNQ 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-
dc.languageEnglish-
dc.publisherELIFE SCIENCES PUBLICATIONS LTD-
dc.subjectRECEPTOR-MEDIATED INHIBITION-
dc.subjectKCNQ2/KCNQ3 K+ CHANNELS-
dc.subjectKV7 POTASSIUM CHANNELS-
dc.subjectPHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE-
dc.subjectSYMPATHETIC NEURONS-
dc.subjectSURFACE EXPRESSION-
dc.subjectEPILEPTIC SEIZURES-
dc.subjectLIVING CELLS-
dc.subjectM-CURRENTS-
dc.subjectPIP2-
dc.titleProtein Arginine Methylation Facilitates KCNQ Channel-PIP2 Interaction Leading to Seizure Suppression-
dc.typeArticle-
dc.identifier.wosid000380842000001-
dc.identifier.scopusid2-s2.0-84983546526-
dc.type.rimsART-
dc.citation.volume5-
dc.citation.publicationnameeLife-
dc.identifier.doi10.7554/eLife.17159-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.contributor.localauthorSohn, Jong-Woo-
dc.contributor.nonIdAuthorKim, Hyun-Ji-
dc.contributor.nonIdAuthorJeong, Myong-Ho-
dc.contributor.nonIdAuthorKim, Kyung-Ran-
dc.contributor.nonIdAuthorJung, Chang-Yun-
dc.contributor.nonIdAuthorLee, Seul-Yi-
dc.contributor.nonIdAuthorKim, Hanna-
dc.contributor.nonIdAuthorKoh, Jewoo-
dc.contributor.nonIdAuthorVuong, Tuan Anh-
dc.contributor.nonIdAuthorPark, Su-Kyung-
dc.contributor.nonIdAuthorChoi, Dahee-
dc.contributor.nonIdAuthorKim, Sung Hun-
dc.contributor.nonIdAuthorKang, KyeongJin-
dc.contributor.nonIdAuthorPark, Joo Min-
dc.contributor.nonIdAuthorJeon, Daejong-
dc.contributor.nonIdAuthorKoo, Seung-Hoi-
dc.contributor.nonIdAuthorHo, Won-Kyung-
dc.contributor.nonIdAuthorKang, Jong-Sun-
dc.contributor.nonIdAuthorKim, Seong-Tae-
dc.contributor.nonIdAuthorCho, Hana-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusRECEPTOR-MEDIATED INHIBITION-
dc.subject.keywordPlusKCNQ2/KCNQ3 K+ CHANNELS-
dc.subject.keywordPlusKV7 POTASSIUM CHANNELS-
dc.subject.keywordPlusPHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE-
dc.subject.keywordPlusSYMPATHETIC NEURONS-
dc.subject.keywordPlusSURFACE EXPRESSION-
dc.subject.keywordPlusEPILEPTIC SEIZURES-
dc.subject.keywordPlusLIVING CELLS-
dc.subject.keywordPlusM-CURRENTS-
dc.subject.keywordPlusPIP2-
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