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Title
Shank3 regulates striatal synaptic abundance of Cyld, a deubiquitinase specific for Lys63-linked polyubiquitin chains
Author(s)
강효진한기훈김진영김윤희장인화윤기나김신현진춘매이연금
Publisher
Wiley-Blackwell
Publication Year
2019-06-19
Abstract
AbstractThe SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins are core organizers of the postsynaptic density in neuronal excitatory synapses, and their defects cause various neurodevelopmental and neuropsychiatric disorders. Mechanistically, Shank3 directly and indirectly interacts with hundreds of synaptic proteins with diverse functions and potentially exerts its regulatory roles in synaptic development and function via these interactors. However, Shank3‐dependent regulation of synaptic abundance has been validated in vivo for only a few Shank3 interactors. Here, using a quantitative proteomic analysis, we identified 136 proteins with altered synaptic abundance in the striatum of Shank3‐overexpressing transgenic (TG) mice. By comparing these proteins with those found in a previous analysis of the postsynaptic density of Shank3 knock‐out (KO) striatum, we identified and confirmed that cylindromatosis‐associated deubiquitinase (Cyld), a deubiquitinase specific for Lys63‐linked polyubiquitin chains, was up‐ and down‐regulated in Shank3 TG and KO striatal synapses, respectively. Consistently, we found that the synaptic levels of Lys63‐linked polyubiquitin chains were down‐ and up‐regulated in the Shank3 TG and KO striata, respectively. Furthermore, by isolating and analyzing the synaptic Cyld complex, we generated a Cyld interactome consisting of 103 proteins, which may include Cyld substrates. Bioinformatic analyses suggested associations of the Cyld interactome with a few brain disorders and synaptic functions. Taken together, these results suggest that Shank3 regulates the synaptic abundance of Cyld in the mouse striatum and, thereby, potentially modulates the Lys63‐linked polyubiquitination of striatal synaptic proteins.
Keyword
Shank3; Cyld; 선조체; 유비퀴틴 분해 효소; Lys63- 연결된 polyubiquitin 사슬; striatum; deubiquitinase; Lys63-linked polyubiquitin chain
Journal Title
Journal of Neurochemistry;
Citation Volume
150
ISSN
0022-3042
DOI
10.1111/jnc.14796
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Appears in Collections:
7. KISTI 연구성과 > 학술지 발표논문
URI
https://repository.kisti.re.kr/handle/10580/16072
Fulltext
 https://scienceon.kisti.re.kr/srch/selectPORSrchArticle.do?cn=NART98065829
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