A role for dendritic translation of CaMKIIα mRNA in olfactory plasticity.

A role for dendritic translation of CaMKIIα mRNA in olfactory plasticity.
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DOI:
10.1371/journal.pone.0040133
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Caillé I
Caillé I
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Néant-Fery M;Pérès E;Nasrallah C;Kessner M;Gribaudo S;Greer C;Didier A;Trembleau A;Caillé I

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树突中的局部蛋白质合成有助于学习和记忆中的突触修饰。编码钙/钙调蛋白依赖性激酶II(CaMKII)α亚单位的α是树枝状定位和局部翻译的。在CaMKIIα树突状翻译中断的小鼠中,通过缺失CaMKIIα3‘非编码区,已证实CaMKIIα局部翻译在海马区依赖记忆中的作用。我们研究了CaMKIIα在小鼠嗅球(OB)的树突定位和局部翻译,OB是嗅觉通路的第一个中继器,表现出对嗅觉经验的高度可塑性。CaMKIIα由卵巢颗粒细胞(GC)表达。通过原位杂交和突触小体制备,我们发现CaMKIIα基因在GC树突中运输,并定位于突触,可能在GC突触局部翻译。CaMKIIα基因和蛋白在短暂暴露于新气味后突触定位的增加表明,它们是活动依赖的过程。α受体拮抗剂可抑制CaMKII NMDAm RNA活性诱导的树突状细胞转运,NMDA受体激动剂可模拟其作用。最后,在CaMKIIα3‘非编码区缺失的小鼠中,CaMKIIα基因在OB的树突定位被破坏,嗅觉联想学习严重受损。因此,我们的研究揭示了CaMKIIα局部翻译的一种新的功能形态,作为嗅觉可塑性的重要决定因素。
Local protein synthesis in dendrites contributes to the synaptic modifications underlying learning and memory. The mRNA encoding the α subunit of the calcium/calmodulin dependent Kinase II (CaMKIIα) is dendritically localized and locally translated. A role for CaMKIIα local translation in hippocampus-dependent memory has been demonstrated in mice with disrupted CaMKIIα dendritic translation, through deletion of CaMKIIα 3′UTR. We studied the dendritic localization and local translation of CaMKIIα in the mouse olfactory bulb (OB), the first relay of the olfactory pathway, which exhibits a high level of plasticity in response to olfactory experience. CaMKIIα is expressed by granule cells (GCs) of the OB. Through in situ hybridization and synaptosome preparation, we show that CaMKIIα mRNA is transported in GC dendrites, synaptically localized and might be locally translated at GC synapses. Increases in the synaptic localization of CaMKIIα mRNA and protein in response to brief exposure to new odors demonstrate that they are activity-dependent processes. The activity-induced dendritic transport of CaMKIIα mRNA can be inhibited by an NMDA receptor antagonist and mimicked by an NMDA receptor agonist. Finally, in mice devoid of CaMKIIα 3′UTR, the dendritic localization of CaMKIIα mRNA is disrupted in the OB and olfactory associative learning is severely impaired. Our studies thus reveal a new functional modality for CaMKIIα local translation, as an essential determinant of olfactory plasticity.
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