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PXD053605

PXD053605 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleArf1-dependent LRBA recruitment to Rab4 endosomes is required for endolysosome homeostasis
DescriptionDeleterious mutations in the LRBA (Lipopolysaccharide Responsive Beige-like Anchor protein) gene cause severe childhood immune dysregulation. The clinical manifestations of LRBA deficiency syndrome are highly variable. Thus, the complexity of the symptoms involving multiple organs and the broad range of unpredictable clinical manifestations complicate the choice of therapeutic interventions. Although LRBA has been linked to Rab11-dependent trafficking of the immune checkpoint protein CTLA-4, its precise cellular role remains elusive. We show that LRBA, however, only slightly colocalize with Rab11. Instead, LRBA is recruited by members of the small GTPase Arf protein family to the TGN and to Rab4+ endosomes, where it controls intracellular traffic. In patient-derived fibroblasts, loss of LRBA led to defects in the endosomal pathway yielding the accumulation of enlarged endolysosomes and lysosome secretion. Thus, LRBA appears to regulate flow through the endosomal system on Rab4+ endosomes. Our data strongly suggest functions of LRBA beyond CTLA-4 trafficking and provide a conceptual framework to develop new therapies for LRBA deficiency.
HostingRepositoryMassIVE
AnnounceDate2024-08-30
AnnouncementXMLSubmission_2024-08-30_03:23:58.834.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterdanilo ritz
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF; timsTOF Ultra
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-03 06:50:21ID requested
12024-08-30 03:23:59announced
Publication List
no publication
Keyword List
submitter keyword: LRBA (Lipopolysaccharide Responsive Beige-like Anchor protein), CTLA-4, Arf protein family, severe childhood immune dysregulation
Contact List
Alexander Schmidt
contact affiliationBiozentrum, Universtiy of Basel, 4056 Basel, Switzerland
contact emailalex.schmidt@unibas.ch
lab head
danilo ritz
contact affiliationUniversity of Basel
contact emaildanilo.ritz@unibas.ch
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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