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Kim, Sun Gyun
시냅스 뇌질환 연구단
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Tanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons

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Title
Tanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons
Author(s)
Sun-Gyun Kim; Suho Lee; Kim, Yangsik; Park, Jieun; Woo, Do Yeon; Kim, Dayeon; Yan Li; Wangyong Shin; Kang, Hyunjeong; Yook, Chaehyun; Minji Lee; Kyungdeok Kim; Roh, Junyeop Daniel; Ryu, Jeseung; Hwajin Jung; Um, Seung Min; Yang, Esther; Kim, Hyun; Han, Jinju; Won Do Heo; Eunjoon Kim
Publication Date
2021-05
Journal
NATURE COMMUNICATIONS, v.12, no.1
Publisher
NLM (Medline)
Abstract
mTOR signaling, involving mTORC1 and mTORC2 complexes, critically regulates neural development and is implicated in various brain disorders. However, we do not fully understand all of the upstream signaling components that can regulate mTOR signaling, especially in neurons. Here, we show a direct, regulated inhibition of mTOR by Tanc2, an adaptor/scaffolding protein with strong neurodevelopmental and psychiatric implications. While Tanc2-null mice show embryonic lethality, Tanc2-haploinsufficient mice survive but display mTORC1/2 hyperactivity accompanying synaptic and behavioral deficits reversed by mTOR-inhibiting rapamycin. Tanc2 interacts with and inhibits mTOR, which is suppressed by mTOR-activating serum or ketamine, a fast-acting antidepressant. Tanc2 and Deptor, also known to inhibit mTORC1/2 minimally affecting neurodevelopment, distinctly inhibit mTOR in early- and late-stage neurons. Lastly, Tanc2 inhibits mTORC1/2 in human neural progenitor cells and neurons. In summary, our findings show that Tanc2 is a mTORC1/2 inhibitor affecting neurodevelopment.
URI
https://pr.ibs.re.kr/handle/8788114/9861
DOI
10.1038/s41467-021-22908-4
ISSN
2041-1723
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Social Neuroscience Group(사회성 뇌과학 그룹) > 1. Journal Papers (저널논문)
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > 1. Journal Papers (저널논문)
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