[DEBUG-WINDOW 처리영역 보기]
즐겨찾기  |  뉴스레터  |  오늘의 정보  |  e브릭몰e브릭몰 회원가입   로그인
BRIC홈 한국을 빛내는 사람들
물리적 거리두기 실천
스폰서배너광고 안내  배너1 배너2 배너3 배너4
LABox-과학으로 본 코로나19 (COVID-19)
전체보기 추천논문 상위피인용논문 인터뷰 그이후 한빛사통계
이태선
이태선 (Tae-Sun Lee) 저자 이메일 보기
KAIST, 연세대학교, 기초과학연구원
저자CV 보기
192 KB
 
조회 1815  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Inositol pyrophosphates inhibit synaptotagmin-dependent exocytosis

Tae-Sun Leea,b,c,1, Joo-Young Leed,1, Jae Won Kyunge, Yoosoo Yangf, Seung Ju Parkd, Seulgi Leed, Igor Pavlovicg, Byoungjae Kongh, Yong Seok Jhoi, Henning J. Jessenj, Dae-Hyuk Kweonh, Yeon-Kyun Shink, Sung Hyun Kime,l,2, Tae-Young Yoonb,c,2, and Seyun Kimd,m,2

a
Department of Physics, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea;
bCenter for Nanomedicine, Institute for Basic Science (IBS), Yonsei University, Seoul 30722, Korea;
cYonsei-IBS Institute, Yonsei University, Seoul 30722, Korea;
dDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea;
eDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea;
fBiomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Korea;
gDepartment of Chemistry, University of Zurich, 8057 Zurich, Switzerland;
hDepartment of Genetic Engineering and Center for Human Interface Nanotechnology, Sungkyunkwan University, Suwon 16419, Korea;
iAsia-Pacific Center for Theoretical Physics, Pohang, Gyeongbuk 37673, Korea;
jInstitute of Organic Chemistry, Albert-Ludwigs-University Freiburg, Freiburg 79104, Germany;
kDepartment of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011;
lDepartment of Physiology, School of Medicine, Neurodegeneration Control Research Center, Kyung Hee University, Seoul 02447, Korea;
mKorea Advanced Institute of Science and Technology Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea

Abstract
Inositol pyrophosphates such as 5-diphosphoinositol pentakisphosphate (5-IP7) are highly energetic inositol metabolites containing phosphoanhydride bonds. Although inositol pyrophosphates are known to regulate various biological events, including growth, survival, and metabolism, the molecular sites of 5-IP7 action in vesicle trafficking have remained largely elusive. We report here that elevated 5-IP7 levels, caused by overexpression of inositol hexakisphosphate (IP6) kinase 1 (IP6K1), suppressed depolarization-induced neurotransmitter release from PC12 cells. Conversely, IP6K1 depletion decreased intracellular 5-IP7 concentrations, leading to increased neurotransmitter release. Consistently, knockdown of IP6K1 in cultured hippocampal neurons augmented action potential-driven synaptic vesicle exocytosis at synapses. Using a FRET-based in vitro vesicle fusion assay, we found that 5-IP7, but not 1-IP7, exhibited significantly higher inhibitory activity toward synaptic vesicle exocytosis than IP6. Synaptotagmin 1 (Syt1), a Ca2+ sensor essential for synaptic membrane fusion, was identified as a molecular target of 5-IP7. Notably, 5-IP7 showed a 45-fold higher binding affinity for Syt1 compared with IP6. In addition, 5-IP7-dependent inhibition of synaptic vesicle fusion was abolished by increasing Ca2+ levels. Thus, 5-IP7 appears to act through Syt1 binding to interfere with the fusogenic activity of Ca2+. These findings reveal a role of 5-IP7 as a potent inhibitor of Syt1 in controlling the synaptic exocytotic pathway and expand our understanding of the signaling mechanisms of inositol pyrophosphates.

inositol pyrophosphate, synaptotagmin, synaptic vesicle exocytosis

1T.-S.L. and J.-Y.L. contributed equally to this work.
2To whom correspondence may be addressed.

Author contributions: T.-S.L., J.-Y.L., J.W.K., Y.Y., S.H.K., T.-Y.Y., and S.K. designed research; T.-S.L., J.-Y.L., J.W.K., Y.Y., S.J.P., S.L., and B.K. performed research; I.P. and H.J.J. contributed new reagents/analytic tools; T.-S.L., J.-Y.L., J.W.K., Y.Y., Y.S.J., D.-H.K., Y.-K.S., S.H.K., T.-Y.Y., and S.K. analyzed data; and T.-S.L., J.-Y.L., Y.Y., S.H.K., T.-Y.Y., and S.K. wrote the paper.


 

논문정보 F1000선정
- 형식: Research article
- 게재일: 2016년 06월 (BRIC 등록일 2016-07-01)
- 연구진: 국내(교신)+국외 연구진태극기
- 분야: Neuroscience
세포 형광 이미징 멀티플렉싱을 위한 초고속 사이클링[Angew. Chem.-Int. Edit.]
고진아
발표: 고진아 (Massachusetts General Ho...)
일자: 2020년 4월 14일 (화) 오전 10시 (한국시간)
언어: 영어
참석자 접수신청하기
The presenting symptoms of cancer and stage at diagnosis[Lancet Oncol.]
구민정
발표: 구민정 (University College Londo...)
일자: 2020년 4월 20일 (월) 오후 04시 (한국시간)
언어: 영어
참석자 접수신청하기

  댓글 0
등록
 
목록
이화여자대학교
관련링크
이태선 님 전체논문보기 >
관련인물
김성현 (경희대학교 의과대학)
김세윤 (KAIST)
윤태영 (서울대학교 생명과학부)
이주용 (KAIST)
관련분야 논문보기
Neuroscience

외부링크
Google (by Tae-Sun Lee)
Pubmed (by Tae-Sun Lee)
프리미엄 Bio일정 Bio일정 프리미엄 안내
[BRIC Webinar]세포 형광 이미징 멀티플렉싱을 위한 초고속 사이클링[Angew. Chem.-Int. Edit.]
[재직자무료교육] 분석기기(HPLC) 활용 품질검사 실습(4.9~4.10) / 화장품 제형제조 기술 실습(4.13~4.14)
[재직자무료교육] 분석기기(HPLC) 활용 품질검사 실습(4.9~4.10) / 화장품 제형제조 기술 실습(4.13~4.14)
날짜: 2020.04.09~14
장소: 충청북도 청주시 흥덕구 오송읍 오송생명1로 194-41 충북산학융합본부 기업연구1관 교육장
[BRIC Webinar]새로운 염기서열 분석방법(BTSeq)을 이용한 hCoV-19 전장유전체 염기서열의 동정 [CELEMICS]
위로가기
한빛사 홈  |  한빛사FAQ  |  한빛사 문의 및 제안
 |  BRIC소개  |  이용안내  |  이용약관  |  개인정보처리방침  |  이메일무단수집거부
Copyright © BRIC. All rights reserved.  |  문의 member@ibric.org
트위터 트위터    페이스북 페이스북   유튜브 유튜브    RSS서비스 RSS
머크