A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis.
A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis.
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DOI：
10.1038/ncb1876
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发表时间：
2009-06
影响因子：
21.3
通讯作者：
Schratt, Gerhard M.
中科院分区：
文献类型：
--
作者：
Siegel, Gabriele;Obernosterer, Gregor;Fiore, Roberto;Oehmen, Martin;Bicker, Silvia;Christensen, Mette;Khudayberdiev, Sharof;Leuschner, Philipp F.;Busch, Clara J. L.;Kane, Christina;Huebel, Katja;Dekker, Frank;Hedberg, Christian;Rengarajan, Balamurugan;Drepper, Carsten;Waldmann, Herbert;Kauppinen, Sakari;Greenberg, Michael E.;Draguhn, Andreas;Rehmsmeier, Marc;Martinez, Javier;Schratt, Gerhard M.
microRNA通路参与了突触蛋白合成的调节，并最终参与了树突棘形态发生，这是一种与持久记忆形式相关的现象。然而，所涉及的特定microRNA（miRNAs）在很大程度上是未知的。我们进行了功能筛选，以确定特定的miRNA，在突触功能，控制树突棘结构。其中一种已鉴定的miRNAs，miR-138，在大脑中高度富集，定位于树突内，并负调节大鼠海马神经元树突棘的大小。miR-138控制酰基蛋白硫酯酶1（APT 1）的表达，APT 1是一种调节已知在突触处起作用的蛋白质（包括G蛋白α亚基（Gα））的棕榈酰化状态的酶。RNAi介导的APT 1敲除和膜定位Gα表达均抑制了miR-138抑制引起的棘增大，表明APT 1调节的Gα脱棕榈酰化可能是miR-138功能的重要下游事件。我们的研究结果揭示了神经元中一种新的miRNA依赖性机制，并证明了以前未被认识到的树突棘形态发生的miRNA依赖性控制的复杂性。
The microRNA pathway has been implicated in the regulation of synaptic protein synthesis and ultimately dendritic spine morphogenesis, a phenomenon associated with long-lasting forms of memory. However, the particular microRNAs (miRNAs) involved are largely unknown. We performed a functional screen to identify specific miRNAs that function at synapses to control dendritic spine structure. One of the identified miRNAs, miR-138, is highly enriched in the brain, localized within dendrites and negatively regulates the size of dendritic spines in rat hippocampal neurons. miR-138 controls the expression of Acyl protein thioesterase 1 (APT1), an enzyme regulating the palmitoylation status of proteins that are known to function at the synapse, including G protein alpha subunits (Gα). RNAi-mediated knockdown of APT1 and expression of membrane-localized Gα both suppress spine enlargement caused by miR-138 inhibition, suggesting that APT1-regulated depalmitoylation of Gα might be an important downstream event of miR-138 function. Our results uncover a novel miRNA-dependent mechanism in neurons and demonstrate a previously unrecognized complexity of miRNA-dependent control of dendritic spine morphogenesis.
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影响因子：
4.5
作者：
Kye, Min-Jeong;Liu, Tsunglin;Kosik, Kenneth S.
通讯作者：
Kosik, Kenneth S.
影响因子：
16.2
作者：
Nägerl, UV;Eberhorn, N;Bonhoeffer, T
通讯作者：
Bonhoeffer, T
影响因子：
64.5
作者：
Ashraf, SI;McLoon, AL;Kunes, S
通讯作者：
Kunes, S
DOI：
10.1016/j.biocel.2006.11.011
发表时间：
2007-01-01
影响因子：
4
作者：
Bernard, Ora
通讯作者：
Bernard, Ora
影响因子：
4.5
作者：
Meister, G;Landthaler, M;Tuschl, T
通讯作者：
Tuschl, T