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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\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAc binding activity derived from\n                    <jats:italic>Clostridium perfringens<\/jats:italic>\n                    OGA (\n                    <jats:italic>Cp<\/jats:italic>\n                    OGA) with TurboID proximity labeling in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , we developed an\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAcylation profiling tool that translates\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAc interactome in major brain regions of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    and found that components of the translational machinery, particularly ribosomal subunits, were abundantly\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAcylated in the mushroom body of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    brain. Hypo-\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAcylation induced by ectopic expression of active\n                    <jats:italic>Cp<\/jats:italic>\n                    OGA 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\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAcylation in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , and suggests a possibility that\n                    <jats:italic>O-<\/jats:italic>\n                    GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.\n                  <\/jats:p>","DOI":"10.7554\/elife.91269","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T10:15:07Z","timestamp":1710497707000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.91269","source":"Crossref","is-referenced-by-count":8,"title":["Tissue-specific O-GlcNAcylation profiling identifies substrates in translational machinery in Drosophila mushroom body contributing to olfactory 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