{
  "abstract": "The Golgi complex serves as the central hub of the biosynthetic pathway, where anterograde and retrograde trafficking converge. How cargo and Golgi-resident proteins traverse this organelle has long been debated. Recent studies have identified a molecular machinery that sorts resident proteins into retrograde-directed COPI vesicles during cisternal maturation. Golgi phosphoprotein 3 (GOLPH3) is a key component of this system; however, its physiological relevance and regulatory mechanisms remain poorly defined. Here, we show that GOLPH3 depletion in mice alters both protein and lipid glycosylation, causes partially penetrant embryonic lethality, and severely impairs growth and bone mineralization. At the molecular level, we find that GOLPH3 is regulated by functionally antagonistic S-acylation events that control the topology of its membrane association. To mediate retrograde trafficking of Golgi-resident glycosyltransferases, GOLPH3 must bind their cytosolic tails. This occurs via a negatively charged surface region, which is correctly oriented only in one of the S-acylated GOLPH3 conformations. Together, these findings reveal a lipid-mediated regulatory mechanism for intra-Golgi trafficking and establish the critical role of GOLPH3 in vertebrate development.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland",
    "Laboratory of Lipid Cell Biology, Institute of Bioengineering and Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland",
    "Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland",
    "Institute of Genetics and Biophysics, National Research Council, Naples, Italy",
    "Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic",
    "Copenhagen Center for Glycocalyx Research, Departments of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark",
    "Laboratory of Regenerative Hematopoiesis, Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland",
    "Laboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland",
    "Hematology Service, Departments of Oncology and Laboratory Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland",
    "Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland. gisou.vandergoot@epfl.ch",
    "Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. matteo.dalperaro@epfl.ch"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Anastasia Theodoropoulou"
    },
    {
      "affs": [
        1
      ],
      "name": "Anita Nasrallah",
      "orcid": "0000-0002-0360-5844"
    },
    {
      "affs": [
        0
      ],
      "name": "Luciano A. Abriata",
      "orcid": "0000-0003-3087-8677"
    },
    {
      "affs": [
        2
      ],
      "name": "Laurence Abrami",
      "orcid": "0000-0002-1774-0481"
    },
    {
      "affs": [
        1
      ],
      "name": "Juliane Da Graça",
      "orcid": "0000-0002-1879-617X"
    },
    {
      "affs": [
        1
      ],
      "name": "Irmak Kaysudu",
      "orcid": "0000-0002-7563-2972"
    },
    {
      "affs": [
        3
      ],
      "name": "Francesco Talotta"
    },
    {
      "affs": [
        0
      ],
      "name": "María J. Marcaida",
      "orcid": "0000-0003-0663-5309"
    },
    {
      "affs": [
        2
      ],
      "name": "Muhammad U. Anwar"
    },
    {
      "affs": [
        4
      ],
      "name": "Ondrej Kováč"
    },
    {
      "affs": [
        5
      ],
      "name": "Sergey Y. Vakhrushev",
      "orcid": "0000-0002-0418-5765"
    },
    {
      "affs": [
        6
      ],
      "name": "Alejandro Alonso Calleja",
      "orcid": "0000-0003-0864-5375"
    },
    {
      "affs": [
        1
      ],
      "name": "Sylvia Ho",
      "orcid": "0000-0002-2969-7329"
    },
    {
      "affs": [
        1
      ],
      "name": "Antonino Asaro",
      "orcid": "0000-0001-9610-5381"
    },
    {
      "affs": [
        2
      ],
      "name": "Francisco Sarmento Mesquita",
      "orcid": "0000-0002-3777-825X"
    },
    {
      "affs": [
        1
      ],
      "name": "Leila Haj Abdullah Alieh",
      "orcid": "0000-0001-5706-2606"
    },
    {
      "affs": [
        1
      ],
      "name": "Charlotte Julie Caroline Gehin",
      "orcid": "0000-0003-1164-2968"
    },
    {
      "affs": [
        2
      ],
      "name": "Lucie Josepha Bracq",
      "orcid": "0000-0001-5909-7984"
    },
    {
      "affs": [
        1
      ],
      "name": "Nika Gorsek",
      "orcid": "0009-0005-5966-2193"
    },
    {
      "affs": [
        0
      ],
      "name": "Sarah Vacle"
    },
    {
      "affs": [
        0
      ],
      "name": "Arthur Samurkas",
      "orcid": "0000-0002-9358-5938"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessio Prunotto",
      "orcid": "0000-0002-6425-964X"
    },
    {
      "affs": [
        7
      ],
      "name": "Luca Fusar Bassini"
    },
    {
      "affs": [
        4
      ],
      "name": "Miroslav Machala",
      "orcid": "0000-0001-6870-6542"
    },
    {
      "affs": [
        8,
        6
      ],
      "name": "Olaia Naveiras",
      "orcid": "0000-0003-3434-0022"
    },
    {
      "affs": [
        5
      ],
      "name": "Katrine T.-B. G. Schjoldager",
      "orcid": "0000-0002-8592-6763"
    },
    {
      "affs": [
        9
      ],
      "name": "F. Gisou van der Goot",
      "orcid": "0000-0002-8522-274X"
    },
    {
      "affs": [
        10
      ],
      "name": "Matteo Dal Peraro",
      "orcid": "0000-0002-2973-3975"
    },
    {
      "affs": [
        1
      ],
      "name": "Giovanni D’Angelo",
      "orcid": "0000-0002-0734-4127"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1fa0s9r3w8rg4.bib",
  "cited_by": 8,
  "doi": "10.1038/s41467-026-74133-6",
  "fulltext_url": null,
  "id": "1fa0s9r3w8rg4",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-74133-6",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
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      "1307|Cellular transport and secretion"
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  "pdf_url": null,
  "pmcid": "PMC13408441",
  "pmid": "42276998",
  "published": "2026-06-11",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/1fa0s9r3w8rg4.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
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      "url": "https://doi.org/10.1038/s41467-026-74133-6"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Cellular transport and secretion",
      "subfield": "cell-biology"
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  ],
  "title": "Molecular regulation and physiological role of GOLPH3-mediated Golgi retention",
  "title_text": "Molecular regulation and physiological role of GOLPH3-mediated Golgi retention",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:30Z",
  "url": "https://research.draconitic.com/paper/1fa0s9r3w8rg4",
  "venue": "Nature Communications",
  "versions": []
}