Laboratory of Neuronal Cell Biology, National Institute for Basic Biology, Okazaki, Japan.
Department of Basic Biology, SOKENDAI, Okazaki, Japan.
Elife. 2017 Nov 21;6:e29677. doi: 10.7554/eLife.29677.
Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks. Genome-wide profiling of mRNA distribution in the hippocampus revealed an underlying mechanism: RNG105 deficiency impaired the asymmetric somato-dendritic localization of mRNAs. Particularly, RNG105 deficiency reduced the dendritic localization of mRNAs encoding regulators of AMPAR surface expression, which was consistent with attenuated homeostatic AMPAR scaling in dendrites and reduced synaptic strength. Thus, RNG105 has an essential role, as a key regulator of dendritic mRNA localization, in long-term memory formation.
局部突触效能的调节被认为对神经元的正常网络连接和记忆形成很重要。全局翻译的失调会影响小鼠的长期记忆，但 RNA 颗粒特异性的局部翻译调节的相关性仍不清楚。在这里，我们证明了 RNG105/caprin1 在长期记忆形成中的作用。在小鼠中敲除 RNG105 会损害海马神经元的突触强度和结构可塑性。此外，RNG105 缺失的小鼠在空间和情境学习任务中的长期记忆形成方面表现出前所未有的严重缺陷。对海马中 mRNA 分布的全基因组分析揭示了一个潜在的机制：RNG105 缺失会损害 mRNAs 的不对称体树突定位。特别是，RNG105 缺失减少了编码 AMPAR 表面表达调节剂的 mRNAs 在树突中的定位，这与树突中稳态 AMPAR 缩放减弱和突触强度降低一致。因此，RNG105 作为树突 mRNA 定位的关键调节剂，在长期记忆形成中起着重要作用。
