The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc.
The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc.
复制标题
天使综合症蛋白 Ube3A 通过泛素化 arc 来调节突触发育。
DOI：
10.1016/j.cell.2010.01.026
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发表时间：
2010-03-05
期刊：
影响因子：
64.5
通讯作者：
Greenberg ME
中科院分区：
文献类型：
--
作者：
Greer PL;Hanayama R;Bloodgood BL;Mardinly AR;Lipton DM;Flavell SW;Kim TK;Griffith EC;Waldon Z;Maehr R;Ploegh HL;Chowdhury S;Worley PF;Steen J;Greenberg ME
Angelman综合征是一种由E3泛素连接酶Ube3A突变引起的衰弱性神经系统疾病，该基因的突变最近也与自闭症谱系障碍（ASDs）有关。Ube3A在神经系统发育过程中的功能，以及Ube3A突变如何引起Angleman综合征和asd患者的认知障碍尚不清楚。我们在这里报道，经验驱动的神经元活动诱导Ube3A转录，然后Ube3A通过控制Arc的降解来调节兴奋性突触的发育，Arc是一种促进谷氨酸受体AMPA亚型内化的突触蛋白。我们发现，神经元中Ube3A功能的破坏导致Arc表达增加，并伴随兴奋性突触中AMPA受体数量的减少。我们认为这种突触AMPA受体表达的失调可能导致了Angelman综合征和其他asd的认知功能障碍。
Angelman Syndrome is a debilitating neurological disorder caused by mutation of the E3 ubiquitin ligase Ube3A, a gene whose mutation has also recently been associated with autism spectrum disorders (ASDs). The function of Ube3A during nervous system development, and how Ube3A mutations give rise to cognitive impairment in individuals with Angleman Syndrome and ASDs are not clear. We report here that experience-driven neuronal activity induces Ube3A transcription and that Ube3A then regulates excitatory synapse development by controlling the degradation of Arc, a synaptic protein that promotes the internalization of the AMPA sub-type of glutamate receptors. We find that disruption of Ube3A function in neurons leads to an increase in Arc expression and a concomitant decrease in the number of AMPA receptors at excitatory synapses. We propose that this deregulation of AMPA receptor expression at synapses may contribute to the cognitive dysfunction that occurs in Angelman Syndrome and possible other ASDs.
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影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
16.2
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
通讯作者：
Worley, Paul F.
DOI：
10.1073/pnas.0707484104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Nakamoto, Mika;Nalavadi, Vijayalaxmi;Warren, Stephen T.
通讯作者：
Warren, Stephen T.