Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA.
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA.
Neuron. 2022 Aug 17;110(16):2588-2606.e6. doi: 10.1016/j.neuron.2022.05.024. Epub 2022 Jun 20.
Learning and memory rely on long-lasting, synapse-specific modifications. Although postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis contributes to presynaptic changes remain unclear. Here, we examined the mouse hippocampal mossy fiber (MF)-CA3 synapse, which expresses both structural and functional presynaptic plasticity and contains presynaptic fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein involved in postsynaptic protein-synthesis-dependent plasticity. We report that MF boutons contain ribosomes and synthesize protein locally. The long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with the translation-dependent enlargement of MF boutons. Remarkably, increasing in vitro or in vivo MF activity enhanced the protein synthesis in MFs. Moreover, the deletion of presynaptic FMRP blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic MF plasticity. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature mammalian brain.
学习和记忆依赖于持久的、突触特异性的修饰。尽管突触后形式的可塑性通常需要局部蛋白质合成，但局部蛋白质合成是否以及如何促进突触前变化尚不清楚。在这里，我们研究了表达结构和功能突触前可塑性的小鼠海马苔藓纤维（MF）-CA3 突触，并含有参与突触后蛋白合成依赖性可塑性的 RNA 结合蛋白突触前脆性 X 信使核糖核蛋白（FMRP）。我们报告说，MF 末梢含有核糖体并进行局部蛋白质合成。MF-CA3 突触传递的长时程增强（MF-LTP）与 MF 末梢的翻译依赖性扩大有关。值得注意的是，增加体外或体内 MF 活性会增强 MF 中的蛋白质合成。此外，突触前 FMRP 的缺失阻断了结构和功能 MF-LTP，表明 FMRP 是突触前 MF 可塑性的关键调节因子。因此，突触前 FMRP 和蛋白质合成动态控制成熟哺乳动物大脑中的突触前结构和功能。
