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Proteomic mapping of organ secretomes using in vivo proximity labeling

ABSTRACT: Identifying an animal's complete set of secreted proteins (secretome), as well as deciphering their tissues of origin, is extremely challenging. To address this, we used a proximity labeling (TurboID) and mass spectrometry approach to identify blood plasma proteins derived from specific cell-types and organs in Drosophila melanogaster larvae. We identified 535 proteins from 10 major cell/tissue types (e.g. muscle, adipose, glia), including most known fly blood proteins. We confirmed the quality of this dataset, using a combination of single cell RNA sequencing (scRNAseq) and CRISPR/Cas9 knock-in fly lines. Our dataset contains hundreds of uncharacterized secreted proteins, many of which originate from a single cell-type/tissue, including some from less appreciated sources (e.g. glia, oenocytes). In addition, we discover proteins that are deposited in a different tissue than where they are synthesized, suggesting travel through circulation and potential inter-organ functions. Our secretome map will serve as a resource to investigate blood protein function, discover novel tissue-tissue communication signals, and mine for homologues of human biomarkers.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Drosophila Melanogaster (ncbitaxon:7227)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000098658 | MassIVE | Mon Jul 28 09:51:00 BST 2025

REPOSITORIES: MassIVE

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