Modulation of dendritic AMPA receptor mRNA trafficking by RNA splicing and editing.
Modulation of dendritic AMPA receptor mRNA trafficking by RNA splicing and editing.
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DOI：
10.1093/nar/gks1223
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发表时间：
2013-01-07
影响因子：
14.9
通讯作者：
Barbon A
中科院分区：
文献类型：
--
作者：
La Via L;Bonini D;Russo I;Orlandi C;Barlati S;Barbon A
RNA转运到树突和局部翻译是高级神经元功能的关键过程。到目前为止，已经在树突中检测到几个α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate受体(AMPAR)mRNAs，并受到局部蛋白质合成的影响。在这里，我们报告了通过突触神经体分析，所有AMPAR GluA1-4mRNAs存在于大鼠海马和皮质突触棘中。特别是，我们证明了树突状AMPAR mRNAs存在于皮质和海马区的翻转版本中。为了进一步证实这些数据，我们利用原位杂交证明了GluA2翻转异构体在体外和体内的树突定位，而触发器变体主要限于胞体。此外，我们报道了树突状AMPA mRNAs在其R/G位点被低水平编辑；使用嵌合GluA2 DNA载体的转染实验也支持这一结果，表明与编辑-翻转版本相比，在R/G位点携带未编辑核苷酸的转录本与Flip外显子结合，更有效地靶向树突状。我们的数据表明，RNA剪接、编辑和运输等转录后调控可能是相互协调的，不同AMPAR亚型在树突中的定位可能在神经元传递的调节中发挥功能作用。
RNA trafficking to dendrites and local translation are crucial processes for superior neuronal functions. To date, several α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) mRNAs have been detected in dendrites and are subject to local protein synthesis. Here, we report the presence of all AMPAR GluA1-4 mRNAs in hippocampal and cortical rat synaptic spines by synaptoneurosomes analysis. In particular, we showed that dendritic AMPAR mRNAs are present in the Flip versions in the cortex and hippocampus. To further confirm these data, we demonstrate, using in situ hybridization, the dendritic localization of the GluA2 Flip isoform in vitro and in vivo, whereas the Flop variant is restricted mainly to the soma. In addition, we report that dendritic AMPA mRNAs are edited at low levels at their R/G sites; this result was also supported with transfection experiments using chimeric GluA2 DNA vectors, showing that transcripts carrying an unedited nucleotide at the R/G site, in combination with the Flip exon, are more efficiently targeted to dendrites when compared with the edited-Flip versions. Our data show that post-transcriptional regulations such as RNA splicing, editing and trafficking might be mutually coordinated and that the localization of different AMPAR isoforms in dendrites might play a functional role in the regulation of neuronal transmission.
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影响因子：
--
作者：
Bergles DE;Jabs R;Steinhäuser C
通讯作者：
Steinhäuser C
影响因子：
11.4
作者：
Huang, Yi-Shuian;Kan, Ming-Chung;Richter, Joel D.
通讯作者：
Richter, Joel D.
DOI：
10.1016/s0169-328x(03)00317-6
发表时间：
2003-10-07
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Barbon, A;Vallini, I;Barlati, S
通讯作者：
Barlati, S
影响因子：
3.4
作者：
Grosskreutz, J;Zoerner, A;Bufler, J
通讯作者：
Bufler, J
影响因子：
4.2
作者：
Barbon, Alessandro;Caracciolo, Luca;Barlati, Sergio
通讯作者：
Barlati, Sergio