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Splice-dependent trans-synaptic PTPδ–IL1RAPL1 interaction regulates synapse formation and non-REM sleep

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Title
Splice-dependent trans-synaptic PTPδ–IL1RAPL1 interaction regulates synapse formation and non-REM sleep
Author(s)
Haram Park; Yeonsoo Choi; Hwajin Jung; Seoyeong Kim; Suho Lee; Hyemin Han; Hanseul Kweon; Suwon Kang; Woong Seob Sim; Frank Koopmans; Esther Yan; Hyun Kim; August B Smit; Yong Chul Bae; Eunjoon Kim
Publication Date
2020-06
Journal
EMBO JOURNAL, v.39, no.11, pp.e104150 - e104150
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020 The Authors. Published under the terms of the CC BY 4.0 licenseAlternative 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
URI
https://pr.ibs.re.kr/handle/8788114/7198
ISSN
0261-4189
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
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