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<p>Synapses are specialized intercellular connections where neurons transfer information, and they are fundamental 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 <i>C. elegans</i>. However, the underlying molecular mechanisms remain largely unknown. In this study, we found that OGT-1, the <i>C. elegans</i> 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.</p>

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O-GlcNAc transferase promotes synaptic assembly independent of catalytic activity in C. elegans

  • 期刊论文

  • 发表日期：

    2025年3月17日

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  • Mengting Wu,
  • Huihui Jiang,
  • Qian Li,
  • Yunhe Liu,
  • Hongjun Zhang,
  • Zhiyong Shao

摘要

Synapses are specialized intercellular connections where neurons transfer information, and they are fundamental 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 C. elegans. However, the underlying molecular mechanisms remain largely unknown. In this study, we found that OGT-1, the C. elegans 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.