PXD043827

PXD043827 is an original dataset announced via ProteomeXchange.

Title	Loss of POGLUT2 and 3 eliminates O-glucose at predicted sites but does not alter other modifications on EGFs
Description	Fibrillins 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.
HostingRepository	PanoramaPublic
AnnounceDate	2024-06-10
AnnouncementXML	Submission_2024-06-10_13:35:38.455.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Daniel Williamson
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Deamidated; dHex; Hex; HexNAc; Oxidation; Hex(1)HexNAc(1); Carbamidomethyl
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-16 22:40:17	ID requested
⏵ 1	2024-06-10 13:35:39	announced

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]

submitter keyword: POGLUT2, POGLUT3, O-glycosylation, mouse, primary fibroblasts, fibrillin-1, extracellular

Robert S. Haltiwanger
contact affiliation	University of Georgia Complex Carbohydrate Research Center
contact email	rhalti@uga.edu
lab head
Daniel Williamson
contact affiliation	University of Georgia Complex Carbohydrate Research Center Department of Biochemistry and Molecular Biology
contact email	dw49986@uga.edu
dataset submitter

Panorama Public dataset URI