Doctoral Program in Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Division of Hematology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell Rep. 2024 Oct 22;43(10):114747. doi: 10.1016/j.celrep.2024.114747. Epub 2024 Sep 18.
The formation, stabilization, and elimination of synapses are tightly regulated during neural development and into adulthood. Pumilio RNA-binding proteins regulate the translation and localization of many synaptic mRNAs and are developmentally downregulated in the brain. We found that simultaneous downregulation of Pumilio 1 and 2 increases both excitatory and inhibitory synapse density in primary hippocampal neurons and promotes synapse maturation. Loss of Pum1 and Pum2 in the mouse brain was associated with an increase in mRNAs involved in mitochondrial function and synaptic translation. These findings reveal a role for developmental Pumilio downregulation as a permissive step in the maturation of synapses and suggest that modulation of Pumilio levels is a cell-intrinsic mechanism by which neurons tune their capacity for synapse stabilization.
在神经发育和成年期，突触的形成、稳定和消除受到严格调控。Pumilio RNA 结合蛋白调节许多突触 mRNA 的翻译和定位，并在大脑中发育下调。我们发现，同时下调 Pumilio 1 和 2 会增加原代海马神经元中兴奋性和抑制性突触的密度，并促进突触成熟。小鼠大脑中 Pum1 和 Pum2 的缺失与参与线粒体功能和突触翻译的 mRNA 增加有关。这些发现揭示了发育下调 Pumilio 作为突触成熟的许可步骤的作用，并表明调节 Pumilio 水平是神经元调节其稳定突触能力的细胞内机制。
