RNG105 Deficiency Impairs the Dendritic Localization of mRNAs for Na+/K+ ATPase Subunit Isoforms and Leads to the Degeneration of Neuronal Networks
RNG105 Deficiency Impairs the Dendritic Localization of mRNAs for Na+/K+ ATPase Subunit Isoforms and Leads to the Degeneration of Neuronal Networks
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DOI：
10.1523/jneurosci.6386-09.2010
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发表时间：
2010-09-22
影响因子：
5.3
通讯作者：
Tokunaga, Makio
中科院分区：
文献类型：
--
作者：
Shiina, Nobuyuki;Yamaguchi, Kazuhiko;Tokunaga, Makio
树突中的mRNA转运和局部翻译在使用依赖性突触修饰和高级脑功能中起关键作用。RNG 105是一种RNA结合蛋白，先前已被鉴定为介导树突状mRNA定位和局部翻译的RNA颗粒的组分。在这里，我们证明小鼠中RNG 105敲除减少了Na+/K+ ATP酶（NKA）亚基同种型的mRNA的树突定位（即，α 3、FXYD 1、FXYD 6和FXYD 7）。树突mRNA定位的丧失伴随着树突中NKA功能的丧失，而不影响索马中的NKA功能。此外，我们表明，RNG 105缺陷影响突触和神经元网络的形成和维持。这些表型的部分原因是抑制NKA，这是已知的影响突触功能以及神经毒性的易感性。本研究首次证明了RNG 105在mRNA树突定位中的体内作用，并揭示了树突mRNA定位与功能网络的发展和维持之间的新联系。
mRNA transport and local translation in dendrites play key roles in use-dependent synaptic modification and in higher-order brain functions. RNG105, an RNA-binding protein, has previously been identified as a component of RNA granules that mediate dendritic mRNA localization and local translation. Here, we demonstrate that RNG105 knock-out in mice reduces the dendritic localization of mRNAs for Na+/K+ ATPase (NKA) subunit isoforms (i.e., alpha 3, FXYD1, FXYD6, and FXYD7). The loss of dendritic mRNA localization is accompanied by the loss of function of NKA in dendrites without affecting the NKA function in the soma. Furthermore, we show that RNG105 deficiency affects the formation and maintenance of synapses and neuronal networks. These phenotypes are partly explained by an inhibition of NKA, which is known to influence synaptic functions as well as susceptibility to neurotoxicity. The present study first demonstrates the in vivo role of RNG105 in the dendritic localization of mRNAs and uncovers a novel link between dendritic mRNA localization and the development and maintenance of functional networks.