PXD049111

PXD049111 is an original dataset announced via ProteomeXchange.

Title	VPS18 Deficiency Leads to a Neutrophil Maturation Defect Associated with Disturbed Vesicle Homeostasis
Description	: Neutrophils, the first cells to arrive at the site of inflammation, are rather short-lived cells and thus have to be constantly replenished. During neutrophil development, vesicle dynamics need to be fine-tuned and impaired vesicle trafficking has been linked to failure in neutrophil maturation. Here, we characterized the role of VPS18 as a central core component of CORVET & HOPS tethering complexes for neutrophil development. Using CRISPR/Cas9-engineered Hoxb8 cells with heterozygous mutations in Vps18, we found that VPS18 deficiency interfered with neutrophil development due to tethering complex instability. As a result, vesicle dynamics were impaired with a strong increase in LC3-II and p62 levels, indicating increased autophagosome formation and reduced autophagic flux. With transmission electron microscopy, we verified the increase in autophagosomes and found irregularly shaped vesicular structures in Vps18 mutants. Subsequently, Vps18 mutant neutrophil progenitors underwent premature apoptosis. We described a novel patient with a heterozygous stop-gain mutation in VPS18 suffering from neutropenia and recurrent infections. To verify our findings in the human system, we used human induced pluripotent stem cells (IPSCs). Here, loss of VPS18 resulted in an almost complete absence of developing neutrophils. Heterozygous VPS18 mutant and patient mutation-harboring IPSCs were characterized by strongly reduced numbers of developing neutrophils. Zebrafish larvae with heterozygous mutations in vps18 were also characterized by significantly reduced neutrophil numbers. This study shows the pivotal impact of VPS18 for adequate vesicle dynamics during neutrophil development which might be relevant in the context of vesicle trafficking during granulopoiesis and congenital neutropenia.
HostingRepository	PRIDE
AnnounceDate	2026-01-28
AnnouncementXML	Submission_2026-01-28_13:01:28.337.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-02 00:52:15	ID requested
⏵ 1	2026-01-28 13:01:28	announced

Dataset with its publication pending

submitter keyword: proteomics, ms,Neutrophils

Felix Meissner
contact affiliation	Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany
contact email	felix.meissner@ukbonn.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2026/01/PXD049111

PRIDE project URI

• PRIDE
  1. PXD049111
     1. Label: PRIDE project
     2. Name: VPS18 Deficiency Leads to a Neutrophil Maturation Defect Associated with Disturbed Vesicle Homeostasis