An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling.
An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling.
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DOI：
10.1016/j.mcn.2009.10.005
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发表时间：
2010-01
影响因子：
3.5
通讯作者：
Wayman, Gary A.
中科院分区：
文献类型：
--
作者：
Impey, Soren;Davare, Monika;Lasiek, Adam;Fortin, Dale;Ando, Hideaki;Varlamova, Olga;Obrietan, Karl;Soderling, Thomas R.;Goodman, Richard H.;Wayman, Gary A.
活动调节的基因表达被认为在神经元回路的发育和完善中起关键作用。然而，调节突触可塑性的转录网络在很大程度上仍未被阐明。我们在此表明，CREB和活动调节的微小RNA（miR132）在活跃的突触发生期间被诱导。此外，miR132对海马棘的形成是必要且充分的。miR132的靶标p250GAP的表达与miR132水平和棘突发生呈负相关。进一步地，敲低p250GAP会增加棘突形成，而引入对miR132无反应的p250GAP突变体则会减弱这种活性。抑制miR132会降低微小兴奋性突触后电流（mEPSC）频率以及GluR1阳性棘突的数量，而敲低p250GAP则有相反的效果。此外，我们表明miR132 / p250GAP回路通过调节突触特异性的Kalirin7 - Rac1信号传导来调节Rac1活性和棘突形成。这些数据表明，神经元活动部分通过增加miR132转录来调节棘突形成，而miR132转录反过来又激活了Rac1 - Pak肌动蛋白重塑途径。
Activity-regulated gene expression is believed to play a key role in the development and refinement of neuronal circuitry. Nevertheless, the transcriptional networks that regulate synaptic plasticity remain largely uncharacterized. We show here that the CREB- and activity-regulated microRNA, miR132, is induced during periods of active synaptogenesis. Moreover, miR132 is necessary and sufficient for hippocampal spine formation. Expression of the miR132 target, p250GAP, is inversely correlated with miR132 levels and spinogenesis. Furthermore, knockdown of p250GAP increases spine formation while introduction of a p250GAP mutant unresponsive to miR132 attenuates this activity. Inhibition of miR132 decreases both mEPSC frequency and the number of GluR1-positive spines, while knockdown of p250GAP has the opposite effect. Additionally, we show that the miR132/p250GAP circuit regulates Rac1 activity and spine formation by modulating synapse-specific Kalirin7-Rac1 signaling. These data suggest that neuronal activity regulates spine formation, in part, by increasing miR132 transcription, which in turn activates a Rac1-Pak actin remodeling pathway.
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
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