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

Autor: Haibin Yu, Dandan Liu, Yaowen Zhang, Ruijun Tang, Xunan Fan, Song Mao, Lu Lv, Fang Chen, Hongtao Qin, Zhuohua Zhang, Daan MF van Aalten, Bing Yang, Kai Yuan
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: eLife, Vol 13 (2024)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.91269
Popis: 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.
Databáze: Directory of Open Access Journals