Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM

Protein O-GlcNAcylation is a prevalent and dynamic post-translational modification that targets a multitude of nuclear and cytoplasmic proteins. Through the modification of diverse substrates, O-GlcNAcylation plays a pivotal role in essential cellular processes, including transcription, translation,...

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Main Authors: Qin Lei, Haibin Yu, Fang Chen, Kai Yuan
Format: Article
Language:English
Published: Bio-protocol LLC 2025-03-01
Series:Bio-Protocol
Online Access:https://bio-protocol.org/en/bpdetail?id=5234&type=0
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author Qin Lei
Haibin Yu
Fang Chen
Kai Yuan
author_facet Qin Lei
Haibin Yu
Fang Chen
Kai Yuan
author_sort Qin Lei
collection DOAJ
description Protein O-GlcNAcylation is a prevalent and dynamic post-translational modification that targets a multitude of nuclear and cytoplasmic proteins. Through the modification of diverse substrates, O-GlcNAcylation plays a pivotal role in essential cellular processes, including transcription, translation, and protein homeostasis. Dysregulation of O-GlcNAc homeostasis has been implicated in a variety of diseases, including cardiovascular diseases, cancer, and neurodegenerative diseases. Studying O-GlcNAcylated proteins in different tissues is crucial to understanding the pathogenesis of these diseases. However, identifying phenotype-relevant candidate substrates in a tissue-specific manner remains unfeasible. We developed a novel tool for the analysis of O-GlcNAcylated proteins, combining a catalytically inactive CpOGA mutant CpOGACD and TurboID proximity labeling technology. This tool converts O-GlcNAc modifications into biotin labeling, enabling the enrichment and mass spectrometry (MS) identification of O-GlcNAcylated proteins in specific tissues. Meanwhile, TurboID-CpOGADM, which carries two point mutations that inactivate both its catalytic and binding activities toward O-GlcNAc modification, was used as a control to differentiate O-GlcNAc-independent protein–protein interactions. We have successfully used TurboID-CpOGACD/DM (TurboID-CpOGAM) to enrich O-GlcNAc proteins in Drosophila combining the UAS/Gal4 system. Our protocol provides a comprehensive workflow for tissue-specific enrichment of candidate O-GlcNAcylated substrates and offers a valuable tool for dissecting tissue-specific O-GlcNAcylation functions in Drosophila.
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spelling doaj-art-1e7cef2d86bd4e8588485f6ebed6824e2025-08-20T02:02:05ZengBio-protocol LLCBio-Protocol2331-83252025-03-0115510.21769/BioProtoc.5234Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAMQin Lei0Haibin Yu1Fang Chen2Kai Yuan3Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital, Central South University, Changsha, ChinaCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, China, Furong Laboratory, 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, ChinaProtein O-GlcNAcylation is a prevalent and dynamic post-translational modification that targets a multitude of nuclear and cytoplasmic proteins. Through the modification of diverse substrates, O-GlcNAcylation plays a pivotal role in essential cellular processes, including transcription, translation, and protein homeostasis. Dysregulation of O-GlcNAc homeostasis has been implicated in a variety of diseases, including cardiovascular diseases, cancer, and neurodegenerative diseases. Studying O-GlcNAcylated proteins in different tissues is crucial to understanding the pathogenesis of these diseases. However, identifying phenotype-relevant candidate substrates in a tissue-specific manner remains unfeasible. We developed a novel tool for the analysis of O-GlcNAcylated proteins, combining a catalytically inactive CpOGA mutant CpOGACD and TurboID proximity labeling technology. This tool converts O-GlcNAc modifications into biotin labeling, enabling the enrichment and mass spectrometry (MS) identification of O-GlcNAcylated proteins in specific tissues. Meanwhile, TurboID-CpOGADM, which carries two point mutations that inactivate both its catalytic and binding activities toward O-GlcNAc modification, was used as a control to differentiate O-GlcNAc-independent protein–protein interactions. We have successfully used TurboID-CpOGACD/DM (TurboID-CpOGAM) to enrich O-GlcNAc proteins in Drosophila combining the UAS/Gal4 system. Our protocol provides a comprehensive workflow for tissue-specific enrichment of candidate O-GlcNAcylated substrates and offers a valuable tool for dissecting tissue-specific O-GlcNAcylation functions in Drosophila.https://bio-protocol.org/en/bpdetail?id=5234&type=0
spellingShingle Qin Lei
Haibin Yu
Fang Chen
Kai Yuan
Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM
Bio-Protocol
title Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM
title_full Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM
title_fullStr Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM
title_full_unstemmed Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM
title_short Tissue-Specific Profiling of O-GlcNAcylated Proteins in Drosophila Using TurboID-CpOGAM
title_sort tissue specific profiling of o glcnacylated proteins in drosophila using turboid cpogam
url https://bio-protocol.org/en/bpdetail?id=5234&type=0
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AT haibinyu tissuespecificprofilingofoglcnacylatedproteinsindrosophilausingturboidcpogam
AT fangchen tissuespecificprofilingofoglcnacylatedproteinsindrosophilausingturboidcpogam
AT kaiyuan tissuespecificprofilingofoglcnacylatedproteinsindrosophilausingturboidcpogam