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PXD043827

PXD043827 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLoss of POGLUT2 and 3 eliminates O-glucose at predicted sites but does not alter other modifications on EGFs
DescriptionFibrillins play a critical role in tissue/organ development and cardiopulmonary function. Here we showed that O-glucosylation of the fibrillins’ epidermal growth factor-like repeats by protein O-glucosyltransferase 2 (POGLUT2) and POGLUT3 was indispensable for in vivo function of mouse fibrillins. Loss of O-glucosylation of fibrillins caused neonatal death with cardiopulmonary, skeletal, and eye defects reminiscent of fibrillin/elastin mutations. Analyses of FBNs in Poglut2/3 double knockout (DKO) lung, and from DKO dermal fibroblast medium and matrix, provided overwhelming evidence that fibrillins were more susceptible than other POGLUT2/3 substrates to loss of O-glucose. In the DKO, defects in microfibril structure impaired elastic fiber formation, reduced TGF-β/pERK signaling, caused structural defects in late gestation lung blood vessels and terminal bronchioles, and impaired cell differentiation and primary septation in the saccules/alveoli. Collectively, these data support an essential role for POGLUT2/3-mediated O-glucosylation in fibrillin trafficking, microfibril assembly/stability, and function in the ECM environment during lung development.
HostingRepositoryPanoramaPublic
AnnounceDate2024-06-10
AnnouncementXMLSubmission_2024-06-10_13:35:38.455.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterDaniel Williamson
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListDeamidated; dHex; Hex; HexNAc; Oxidation; Hex(1)HexNAc(1); Carbamidomethyl
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-16 22:40:17ID requested
12024-06-10 13:35:39announced
Publication List
Neupane S, Williamson DB, Roth RA, Halabi CM, Haltiwanger RS, Holdener BC, Poglut2/3 double knockout in mice results in neonatal lethality with reduced levels of fibrillin in lung tissues. J Biol Chem, 300(7):107445(2024) [pubmed]
Keyword List
submitter keyword: POGLUT2, POGLUT3, O-glycosylation, mouse, primary fibroblasts, fibrillin-1, extracellular
Contact List
Robert S. Haltiwanger
contact affiliationUniversity of Georgia Complex Carbohydrate Research Center
contact emailrhalti@uga.edu
lab head
Daniel Williamson
contact affiliationUniversity of Georgia Complex Carbohydrate Research Center Department of Biochemistry and Molecular Biology
contact emaildw49986@uga.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI