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PXD048503

PXD048503 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleERLIN1 and ERLIN2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway
DescriptionComplexes of ERLIN1 and ERLIN2 form large ring-like cup shaped structures on the endoplasmic reticulum (ER) membrane and serve as platform to bind cholesterol and E3-ubiquitin ligases, potentially defining functional nanodomains. Here, we show that ERLIN scaffolds mediate the interaction between the full-length isoform of TMUB1 and RNF170. We identify a luminal N-terminal conserved region in TMUB1 and RNF170 required for the interaction. Three-dimensional modelling using Alpha Fold Multimer shows that this conserved motif binds the SPFH domain of two adjacent ERLIN subunits at different interfaces. ERLIN1 and ERLIN2 variants that preclude these interactions are unstable and have been previously linked to hereditary spastic paraplegia (HSP), a progressive neurological disorder. Using HeLa cells that lack both ERLINs, we uncovered novel processes dependent on these scaffolds. Proteomics and lipidomics approaches demonstrated a role of ERLINs in cell adhesion, vesicular secretion, and cholesterol and sphingomyelin metabolism. Cells lacking ERLINs displayed collapsed tubular ER, a fragmented Golgi apparatus, and impaired post-Golgi trafficking. Moreover, they accumulated cholesterol esters and triacylglycerols in larger lipid droplets. We found that inhibition of sterol-O-acyltransferase 1 with avasimibe suppressed lipid droplet accumulation, Golgi fragmentation and SREBP activation. We conclude that ERLIN scaffolds maintain cholesterol levels at the ER in check by favouring trafficking to the Golgi over esterification, thereby regulating the secretory pathway.
HostingRepositoryPRIDE
AnnounceDate2024-05-21
AnnouncementXMLSubmission_2024-05-21_02:40:35.652.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPrerana Wagle
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-12 04:49:27ID requested
12024-05-21 02:40:36announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ERLIN2, TMUB1, DRMs, endoplasmic reticulum, Hereditary Spastic Paraplegia,ERLIN1, lipid rafts
Contact List
Elena I. Rugarli
contact affiliationCECAD Research Center, Joseph-Stelzmann Str. 26, 50931, Cologne, Germany
contact emailElena.rugarli@uni-koeln.de
lab head
Prerana Wagle
contact affiliationCECAD Research Center
contact emailproteomics-facility@uni-koeln.de
dataset submitter
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Dataset FTP location
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