The AMPA receptor subunit GluA1 is essential for induction of synaptic plasticity. While various regulatory mechanisms of AMPA receptor expression have been identified, the underlying mechanisms of GluA1 protein synthesis are not fully understood. In neurons, axonal and dendritic mRNAs have been reported to be translated in a cap-independent manner. However, molecular mechanisms of cap-independent translation of synaptic mRNAs remain largely unknown. Here, we show that GluA1 mRNA contains an internal ribosome entry site (IRES) in the 5′UTR. We also demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 interacts with GluA1 mRNA and mediates internal initiation of GluA1. Brain-derived neurotrophic factor (BDNF) stimulation increases IRES-mediated GluA1 translation via up-regulation of HNRNP A2/B1. Moreover, BDNF-induced GluA1 expression and dendritic spine density were significantly decreased in neurons lacking hnRNP A2/B1. Together, our data demonstrate that IRES-mediated translation of GluA1 mRNA is a previously unidentified feature of local expression of the AMPA receptor.

AMPA 受体亚基 GluA1 对突触可塑性的诱导至关重要。虽然已经确定了 AMPA 受体表达的各种调节机制，但 GluA1 蛋白合成的潜在机制尚不完全清楚。据报道，在神经元中，轴突和树突 mRNA 以不依赖于帽的方式进行翻译。然而，突触mRNA的帽非依赖性翻译的分子机制仍然很大程度上未知。在这里，我们显示GluA1 mRNA 在 5'UTR 中包含一个内部核糖体进入位点 (IRES)。我们还证明异质核核糖核蛋白 (hnRNP) A2/B1 与GluA1 mRNA 相互作用并介导GluA1的内部启动. 脑源性神经营养因子 (BDNF) 刺激通过上调 HNRNP A2/B1 增加 IRES 介导的 GluA1 翻译。此外，在缺乏 hnRNP A2/B1 的神经元中，BDNF 诱导的 GluA1 表达和树突棘密度显着降低。总之，我们的数据表明，IRES 介导的GluA1 mRNA 翻译是以前未知的 AMPA 受体局部表达特征。