A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D9BBA487BF83
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.
Journal
eLife
Author(s)
Valoskova K., Biebl J., Roblek M., Emtenani S., Gyoergy A., Misova M., Ratheesh A., Reis-Rodrigues P., Shkarina K., Larsen ISB, Vakhrushev S.Y., Clausen H., Siekhaus D.E.
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
8
Pages
e41801
Language
english
Abstract
Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva's vertebrate ortholog, MFSD1, rescues the minerva mutant's migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.
Keywords
BMP, D. melanogaster, ECM, Extracellular Matrix, MFSD1, Notch, O-glycosylation, Qsox1, T antigen, Tn antigen, cancer biology, developmental biology, dissemination, invasion, macrophage, major facilitator superfamily, metastasis, protein folding, transporter
Pubmed
Web of science
Open Access
Yes
Create date
11/04/2019 10:15
Last modification date
20/08/2019 15:59
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