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Data from: Tissue-specific O-GlcNAcylation profiling identifies substrates in translational machinery in the Drosophila mushroom body contributing to olfactory learning

Yuan, Kai1; Yu, Haibin1; Liu, Dandan2; Zhang, Yaowen3; Tang, Ruijun1; Fan, Xunan3; Mao, Song1; Lv, Lu1; Chen, Fang1; Qin, Hongtao4; Zhang, Zhuohua3; van Aalten, Daan5; Yang, Bing2

Published Apr 12, 2024 on Dryad. https://doi.org/10.5061/dryad.sj3tx969t

Data files

Apr 12, 2024 version files 102.19 MB

Abstract

O-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region-specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived from Clostridium perfringens OGA (CpOGA) with TurboID proximity labeling in Drosophila, we developed an O-GlcNAcylation profiling tool that translates O-GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the O-GlcNAc interactome in major brain regions of Drosophila and found that components of the translational machinery, particularly ribosomal subunits, were abundantly O-GlcNAcylated in the mushroom body of Drosophila brain. Hypo-O-GlcNAcylation induced by ectopic expression of active CpOGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of O-GlcNAcylation in Drosophila and suggests a possibility that O-GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.