M'Angale P Githure, Lemieux Adrienne, Liu Yumeng, Wang Shuhao, Zinter Max, Alegre Gimena, Simkin Alfred, Budnik Vivian, Kelch Brian A, Thomson Travis
Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
PLoS Biol. 2025 Feb 18;23(2):e3002983. doi: 10.1371/journal.pbio.3002983. eCollection 2025 Feb.
Transposons are parasitic genome elements that can also serve as raw material for the evolution of new cellular functions. However, how retrotransposons are selected and domesticated by host organisms to modulate synaptic plasticity remains largely unknown. Here, we show that the Ty1 retrotransposon Copia forms virus-like capsids in vivo and transfers between cells. Copia is enriched at the Drosophila neuromuscular junction (NMJ) and transported across synapses, and disrupting its expression promotes both synapse development and structural synaptic plasticity. We show that proper synaptic plasticity is maintained in Drosophila by the balance of Copia and the Arc1 (activity-regulated cytoskeleton-associated protein) homolog. High-resolution cryogenic-electron microscopy imaging shows that the structure of the Copia capsid has a large capacity and pores like retroviruses but is distinct from domesticated capsids such as dArc1. Our results suggest a fully functional transposon mediates synaptic plasticity, possibly representing an early stage of domestication of a retrotransposon.
转座子是寄生性基因组元件，也可作为新细胞功能进化的原材料。然而，逆转录转座子如何被宿主生物选择并驯化以调节突触可塑性在很大程度上仍不清楚。在这里，我们表明Ty1逆转录转座子Copia在体内形成病毒样衣壳并在细胞间转移。Copia在果蝇神经肌肉接头（NMJ）处富集并跨突触运输，破坏其表达会促进突触发育和突触结构可塑性。我们表明，果蝇通过Copia和Arc1（活性调节细胞骨架相关蛋白）同源物之间的平衡来维持适当的突触可塑性。高分辨率低温电子显微镜成像显示，Copia衣壳的结构具有大容量且像逆转录病毒一样有孔，但与驯化的衣壳如dArc1不同。我们的结果表明，一个功能完整的转座子介导突触可塑性，这可能代表了逆转录转座子驯化的早期阶段。
