Wu Mengting, Jiang Huihui, Li Qian, Liu Yunhe, Zhang Hongjun, Shao Zhiyong
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China.
J Biosci. 2025;50.
Synapses are specialized intercellular connections where neurons transfer information, and they are funda mental for complex brain functions. Synaptic assembly is precisely regulated, and its dysfunction often leads to neurodevelopmental disorders. Previously, we demonstrated that O-GlcNAc transferase (OGT-1) is required for synaptic development in . However, the underlying molecular mechanisms remain largely unknown. In this study, we found that OGT-1, the homolog of mammalian OGT, regulates presynaptic assembly in AIY interneurons in a catalysis-independent manner. Mechanistically, OGT-1 acts upstream of a specific isoform of the transcription factor DAF-16/FOXO in the insulin signaling pathway. Finally, we found that OGT-1 regulates presynaptic assembly in a subset of neurons and is required for associative learning. Our findings provide insights into the role of OGT-1 in synaptic assembly.
突触是神经元传递信息的特殊细胞间连接，它们对于复杂的脑功能至关重要。突触组装受到精确调控，其功能障碍常导致神经发育障碍。此前，我们证明了O-连接N-乙酰葡糖胺转移酶（OGT-1）对于[具体生物]的突触发育是必需的。然而，其潜在的分子机制仍 largely未知。在本研究中，我们发现OGT-1（哺乳动物OGT的同源物）以非催化方式调节AIY中间神经元的突触前组装。从机制上讲，OGT-1在胰岛素信号通路中转录因子DAF-16/FOXO的特定异构体上游起作用。最后，我们发现OGT-1调节一部分神经元的突触前组装，并且是联想学习所必需的。我们的发现为OGT-1在突触组装中的作用提供了见解。
