한빛사논문
- 조회2,811
Haram Park1,†, Yeonsoo Choi1,†, Hwajin Jung1,†, Seoyeong Kim2,†, Suho Lee1, Hyemin Han3, Hanseul Kweon2, Suwon Kang2, Woong Seob Sim2, Frank Koopmans4,5, Esther Yang6, Hyun Kim6, August B Smit5, Yong Chul Bae3 & Eunjoon Kim1,2,*
1Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, Korea
2Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, Korea
3Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea
4Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, Amsterdam, The Netherlands
5Department of Molecular and Cellular Neurobiology, CNCR, VU University and UMC Amsterdam, Amsterdam, The Netherlands
6Department of Anatomy and Division of Brain Korea 21, Biomedical Science, College of Medicine, Korea University, Seoul, Korea
*Corresponding author.
†These authors contributed equally to this work.
Abstract
Alternative splicing regulates trans‐synaptic adhesions and synapse development, but supporting in vivo evidence is limited. PTPδ, a receptor tyrosine phosphatase adhering to multiple synaptic adhesion molecules, is associated with various neuropsychiatric disorders; however, its in vivo functions remain unclear. Here, we show that PTPδ is mainly present at excitatory presynaptic sites by endogenous PTPδ tagging. Global PTPδ deletion in mice leads to input‐specific decreases in excitatory synapse development and strength. This involves tyrosine dephosphorylation and synaptic loss of IL1RAPL1, a postsynaptic partner of PTPδ requiring the PTPδ‐meA splice insert for binding. Importantly, PTPδ‐mutant mice lacking the PTPδ‐meA insert, and thus lacking the PTPδ interaction with IL1RAPL1 but not other postsynaptic partners, recapitulate biochemical and synaptic phenotypes of global PTPδ‐mutant mice. Behaviorally, both global and meA‐specific PTPδ‐mutant mice display abnormal sleep behavior and non‐REM rhythms. Therefore, alternative splicing in PTPδ regulates excitatory synapse development and sleep by modulating a specific trans‐synaptic adhesion.
논문정보
TOP52020년 후보
- Research article
- 2020년 04월 (BRIC 등록일 2020-05-07)
- 국내(교신)+국외 연구진
- 생명과학 > 생리학
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