PXD064301-1

PXD064301 is an original dataset announced via ProteomeXchange.

Title	Molecular Regulation and Physiological Role of GOLPH3-mediated Golgi retention
Description	The Golgi complex serves as the central hub of the biosynthetic pathway, where anterograde and retrograde trafficking fluxes converge. The mechanism by which cargo and Golgi-resident proteins traverse this organelle has long been debated. Recent discoveries have identified a molecular machinery that sorts Golgi-resident proteins into retrograde-directed COPI vesicles during cisternal maturation. Golgi phosphoprotein 3 (GOLPH3) is a key component of this machinery; however, the regulation and physiological relevance of GOLPH3-mediated Golgi retention remain largely uncharacterized. Here, we report that GOLPH3 binds the cytosolic tails of Golgi-resident glycosyltransferases via a negatively charged region on its surface. Productive interaction requires GOLPH3’s association with the Golgi membrane, mediated through an articulated mechanism that involves both specific and non-specific lipid interactions, and is regulated by functionally antagonistic S-acylation events. Moreover, we demonstrate that GOLPH3 depletion in mice leads to defects in protein and lipid glycosylation, resulting in severe impairments in growth and bone mineralization. Altogether, our findings reveal mechanistic regulation of intra-Golgi trafficking and underscore its importance in vertebrate development.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:11:20.996.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergey Vakhrushev
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-26 04:41:49	ID requested
⏵ 1	2026-09-06 16:11:21	announced

10.1038/s41467-026-74133-6;

Theodoropoulou A, Nasrallah A, Abriata LA, Abrami L, Da Gra, ç, a J, Kaysudu I, Talotta F, Marcaida MJ, Anwar MU, Kov, á, č O, Vakhrushev SY, Alonso-Calleja A, Ho S, Asaro A, Mesquita FS, Alieh L, Gehin C, Bracq L, Gor, š, ek N, Vacle S, Samurkas A, Prunotto A, Fusar Bassini L, Machala M, Naveiras O, Schjoldager KT, van der Goot FG, Dal Peraro M, D'Angelo G, Molecular regulation and physiological role of GOLPH3-mediated Golgi retention. Nat Commun, 17(1):(2026) [pubmed]

submitter keyword: Human, glycoproteomics, liver, GOLPH3

Sergey Vakhrushev
contact affiliation	Uni of Copenhagen, Department of Cellular and Molecular Medicine
contact email	seva@sund.ku.dk
lab head
Sergey Vakhrushev
contact affiliation	Department of Cellular and Molecular Medicine
contact email	seva@sund.ku.dk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/09/PXD064301

PRIDE project URI

• PRIDE
  1. PXD064301
     1. Label: PRIDE project
     2. Name: Molecular Regulation and Physiological Role of GOLPH3-mediated Golgi retention