Tissue-specific O-GlcNAcylation profiling identifies substrates in translational machinery in Drosophila mushroom body contributing to olfactory learning
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Dandan Liu
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China
Yaowen Zhang
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Ruijun Tang
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Xunan Fan
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Song Mao
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Lu Lv
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
Hongtao Qin
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, Changsha, China
Zhuohua Zhang
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Daan MF van Aalten
Department of Molecular Biology and Genetics, University of Aarhus, Aarhus, Denmark
Bing Yang
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China
Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China; The Biobank of Xiangya Hospital, Central South University, Changsha, China
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.
