Redox regulation of memory formation by Rrp1 in <i>Drosophila</i>
Abstract
Long-term memory (LTM) formation requires precise gene regulation, yet the role of redox activity in this process remains poorly understood. Here, we identify Drosophila recombination repair protein 1 (Rrp1), a homolog of human apurinic/apyrimidinic endonuclease 1 (APE1), as a key redox regulator of LTM. In paired dorsal-anterior-lateral neurons—critical for aversive olfactory memory—Rrp1 knockdown impairs memory formation, whereas its overexpression enhances retention. Pharmacological inhibition of Rrp1 redox activity with E3330 suppresses Period and CaMKII expression, disrupting LTM formation. Notably, human APE1 redox activity rescues memory deficits in Rrp1-deficient flies, promotes de novo Period synthesis, and facilitates LTM formation. Moreover, Rrp1 is required for CREBA-mediated LTM acceleration, revealing a redox-dependent link between transcriptional regulation and memory persistence. These findings establish Rrp1 as a critical modulator of LTM in Drosophila and highlight redox regulation as a conserved mechanism underlying memory formation.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Cheng-Tzu Hsu
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Chun-Chao Chen
Institute of Precision Medicine, College of Medicine, National Sun Yat-sen University
Yu-Ling Hung
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Ya-Ting Yang
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Yen-Hua Chiu
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Sing-Shien Fong
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Jung-Hsuan Yang
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Zheng-Wen Wu
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Jian-Wei Liou
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Hsuan-Wen Lin
Department of Biomedical Science and Technology, College of Medicine, National Sun Yat-sen University
Kuan-Lin Feng
Brain Research Center, National Tsing Hua University
Jia-Ling Yang
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University
Ann-Shyn Chiang
Institute of Biotechnology and Department of Life Science, National Tsing-Hua University