Degradation of postsynaptic scaffold GKAP and regulation of dendritic spine morphology by the TRIM3 ubiquitin ligase in rat hippocampal neurons.
Degradation of postsynaptic scaffold GKAP and regulation of dendritic spine morphology by the TRIM3 ubiquitin ligase in rat hippocampal neurons.
复制标题
大鼠海马神经元中突触后支架 GKAP 的降解和 TRIM3 泛素连接酶对树突棘形态的调节。
DOI：
10.1371/journal.pone.0009842
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发表时间：
2010-03-24
期刊：
影响因子：
3.7
通讯作者：
Sheng M
中科院分区：
文献类型：
--
作者：
Hung AY;Sung CC;Brito IL;Sheng M
神经元活动的变化改变树突棘的结构，并改变突触的功能和蛋白质组成。泛素-蛋白酶体系统对突触后密度（PSD）蛋白的调控降解被认为在活动依赖性突触重塑中起重要作用。在体外和体内刺激神经元活性诱导GKAP/SAPAP和Shank的泛素化和降解，PSD的主要支架蛋白。然而，具体的泛素连接酶，调节突触后蛋白质的组成还没有确定。在这里，我们确定了环指蛋白TRIM 3作为一个特定的E3泛素连接酶的PSD支架GKAP/SAPAP 1。TRIM 3存在于大鼠脑PSD组分中，刺激GKAP的泛素化和蛋白酶体依赖性降解，并诱导GKAP和相关支架Shank 1从突触后位点丢失。通过RNA干扰（RNAi）抑制内源性TRIM 3导致GKAP和Shank 1在突触处的积累增加，以及树突棘头的增大。TRIM 3的RNAi也防止了由突触活动引起的GKAP的丢失。因此，TRIM 3是一种新型的E3连接酶，其介导PSD支架蛋白的活性依赖性周转，并且是树突棘形态的负调节剂。
Changes in neuronal activity modify the structure of dendritic spines and alter the function and protein composition of synapses. Regulated degradation of postsynaptic density (PSD) proteins by the ubiquitin-proteasome system is believed to play an important role in activity-dependent synaptic remodeling. Stimulating neuronal activity in vitro and in vivo induces the ubiquitination and degradation of GKAP/SAPAP and Shank, major scaffold proteins of the PSD. However, the specific ubiquitin ligases that regulate postsynaptic protein composition have not been identified. Here we identify the RING finger-containing protein TRIM3 as a specific E3 ubiquitin ligase for the PSD scaffold GKAP/SAPAP1. Present in PSD fractions from rat brain, TRIM3 stimulates ubiquitination and proteasome-dependent degradation of GKAP, and induces the loss of GKAP and associated scaffold Shank1 from postsynaptic sites. Suppression of endogenous TRIM3 by RNA interference (RNAi) results in increased accumulation of GKAP and Shank1 at synapses, as well as enlargement of dendritic spine heads. RNAi of TRIM3 also prevented the loss of GKAP induced by synaptic activity. Thus, TRIM3 is a novel E3 ligase that mediates activity-dependent turnover of PSD scaffold proteins and is a negative regulator of dendritic spine morphology.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
DOI：
10.1083/jcb.136.3.669
发表时间：
1997-02-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim E;Naisbitt S;Hsueh YP;Rao A;Rothschild A;Craig AM;Sheng M
通讯作者：
Sheng M
DOI：
10.1006/bbrc.1999.2045
发表时间：
2000-01-27
影响因子：
3.1
作者：
El-Husseini, AED;Kwasnicka, D;Vincent, SR
通讯作者：
Vincent, SR
影响因子：
5.3
作者：
Hung, Albert Y.;Futai, Kensuke;Sheng, Morgan
通讯作者：
Sheng, Morgan
影响因子：
64.8
作者：
KIM, E;NIETHAMMER, M;SHENG, M
通讯作者：
SHENG, M