{"entity": "publication", "iuid": "5b04813932b344c49a30751c70d72dc8", "timestamp": "2026-08-22T06:57:20.245Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5b04813932b344c49a30751c70d72dc8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5b04813932b344c49a30751c70d72dc8"}}, "title": "The S-palmitoylome and DHHC-PAT interactome of Drosophila melanogaster S2R+ cells indicate a high degree of conservation to mammalian palmitoylomes.", "authors": [{"family": "Porcellato", "given": "Elena", "initials": "E", "orcid": "0000-0002-3637-8828", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82c3562a692143c795666a965bd3a601.json"}}, {"family": "Gonz\u00e1lez-S\u00e1nchez", "given": "Juan Carlos", "initials": "JC"}, {"family": "Ahlmann-Eltze", "given": "Constantin", "initials": "C"}, {"family": "Elsakka", "given": "Mahmoud Ali", "initials": "MA"}, {"family": "Shapira", "given": "Itamar", "initials": "I", "orcid": "0000-0002-2175-6806", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e596f287f4e54ee5b4c306531463b140.json"}}, {"family": "Fritsch", "given": "J\u00fcrgen", "initials": "J"}, {"family": "Navarro", "given": "Juan Antonio", "initials": "JA"}, {"family": "Anders", "given": "Simon", "initials": "S", "orcid": "0000-0003-4868-1805", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7a679b62d481464882a9bd395b2afd59.json"}}, {"family": "Russell", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7213-1398", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/848effd2d9ef47cebb6be8539ad9cea9.json"}}, {"family": "Wieland", "given": "Felix T", "initials": "FT"}, {"family": "Metzendorf", "given": "Christoph", "initials": "C", "orcid": "0000-0003-3891-2809", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f4baf8b411d43cb99eca05af8ea5662.json"}}], "type": "journal article", "published": "2022-08-12", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "17", "issue": "8", "pages": "e0261543", "issn-l": "1932-6203"}, "abstract": "Protein S-palmitoylation, the addition of a long-chain fatty acid to target proteins, is among the most frequent reversible protein modifications in Metazoa, affecting subcellular protein localization, trafficking and protein-protein interactions. S-palmitoylated proteins are abundant in the neuronal system and are associated with neuronal diseases and cancer. Despite the importance of this post-translational modification, it has not been thoroughly studied in the model organism Drosophila melanogaster. Here we present the palmitoylome of Drosophila S2R+ cells, comprising 198 proteins, an estimated 3.5% of expressed genes in these cells. Comparison of orthologs between mammals and Drosophila suggests that S-palmitoylated proteins are more conserved between these distant phyla than non-S-palmitoylated proteins. To identify putative client proteins and interaction partners of the DHHC family of protein acyl-transferases (PATs) we established DHHC-BioID, a proximity biotinylation-based method. In S2R+ cells, ectopic expression of the DHHC-PAT dHip14-BioID in combination with Snap24 or an interaction-deficient Snap24-mutant as a negative control, resulted in biotinylation of Snap24 but not the Snap24-mutant. DHHC-BioID in S2R+ cells using 10 different DHHC-PATs as bait identified 520 putative DHHC-PAT interaction partners of which 48 were S-palmitoylated and are therefore putative DHHC-PAT client proteins. Comparison of putative client protein/DHHC-PAT combinations indicates that CG8314, CG5196, CG5880 and Patsas have a preference for transmembrane proteins, while S-palmitoylated proteins with the Hip14-interaction motif are most enriched by DHHC-BioID variants of approximated and dHip14. Finally, we show that BioID is active in larval and adult Drosophila and that dHip14-BioID rescues dHip14 mutant flies, indicating that DHHC-BioID is non-toxic. In summary we provide the first systematic analysis of a Drosophila palmitoylome. We show that DHHC-BioID is sensitive and specific enough to identify DHHC-PAT client proteins and provide DHHC-PAT assignment for ca. 25% of the S2R+ cell palmitoylome, providing a valuable resource. In addition, we establish DHHC-BioID as a useful concept for the identification of tissue-specific DHHC-PAT interactomes in Drosophila.", "doi": "10.1371/journal.pone.0261543", "pmid": "35960718", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9374236"}, {"db": "pii", "key": "PONE-D-21-38223"}], "notes": [], "created": "2026-08-21T12:52:17.531Z", "modified": "2026-08-21T12:52:17.688Z"}