Structural Biology Center, National Institute of Genetics, Research Organization of Information and Systems, and Department of Genetics, Sokendai, Mishima, Shizuoka 411-8540, Japan.
J Neurosci. 2010 Sep 22;30(38):12816-30. doi: 10.1523/JNEUROSCI.6386-09.2010.
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., α3, 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.
mRNA 在树突中的运输和局部翻译在依赖于使用的突触修饰和更高阶的大脑功能中发挥关键作用。RNG105 是一种 RNA 结合蛋白，先前已被鉴定为介导树突 mRNA 定位和局部翻译的 RNA 颗粒的组成部分。在这里，我们证明在小鼠中敲除 RNG105 会减少 Na+/K+ATP 酶 (NKA) 亚基异构体 (即 α3、FXYD1、FXYD6 和 FXYD7) 的树突 mRNA 定位。树突 mRNA 定位的丧失伴随着 NKA 在树突中的功能丧失，而不影响 NKA 在胞体中的功能。此外，我们表明 RNG105 缺乏会影响突触和神经元网络的形成和维持。这些表型部分可以通过 NKA 的抑制来解释，已知 NKA 会影响突触功能以及对神经毒性的易感性。本研究首次证明了 RNG105 在树突 mRNA 定位中的体内作用，并揭示了树突 mRNA 定位与功能网络的发育和维持之间的新联系。
