Regulation of synapse development and function by the synaptic adhesion molecule NGL-3시냅스 접착 단백질 NGL-3 에 의한 시냅스 발달과 기능 조절에 관한 연구

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Synaptic adhesion molecules are thought to contribute to the development, function, and plasticity of neuronal synapses largely through their trans-synaptic synaptic adhesions. I found here that NGL-3 (netrin-G ligand-3), a postsynaptic adhesion molecule that trans-synaptically interacts with the LAR family of receptor tyrosine phosphatases and intracellularly with the postsynaptic scaffolding protein PSD-95, undergoes a proteolytic cleavage process. NGL-3 cleavage is induced by NMDA treatment in cultured neurons or low frequency stimulation in brain slices, and requires the activities of NMDA glutamate receptors, matrix metalloproteinases (MMPs), and presenilin/$\gamma$-secretase. NGL-3 mutant (Ngl3$^{-/-}$ mice) mice show normal synaptic transmission, but impaired long term potentiation and depression. Behaviorally, Ngl3$^{-/-}$ mice showed hyperactivity, anxiolytic-like behaviors, and impaired learning and memory. Hyperactivity of Ngl3$^{-/-}$ mice is partially rescued by D-cycloserine, a partial NMDA receptor agonist, whereas anxiolytic-like behaviors are not. These results suggest that NGL-3 is a novel substrate of MMPs and $\gamma$-secretase and that NGL-3 cleavage may regulate synaptic adhesion during NMDA-dependent LTD. NGL-3 is important for normal brain development, synaptic plasticity, locomotion, anxiety-like behavior, and learning and memory in vivo. Lastly, these results suggest that reduced NMDA receptor activity may lead to hyperactivity in Ngl3$^{-/-}$ mice.
Advisors
Kim, Eun Joonresearcher김은준researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2016
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2016.2,[vii, 135 p. :]

Keywords

neuroscience▼asynapse▼aadhesion molecule▼aNGL-3▼acleavage; 신경과학▼a시냅스▼a접착단백질▼a동물행동분석▼a절단

URI
http://hdl.handle.net/10203/264774
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=849814&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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