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

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Valoskova, Katarina, Biebl, Julia, Roblek, Marko, Emtenani, Shamsi, Gyoergy, Attila, Misova, Michaela, Ratheesh, Aparna, Reis-Rodrigues, Patricia, Shkarina, Kateryna, Larsen, Ida Signe Bohse, Vakhrushev, Sergey Y., Clausen, Henrik and Siekhaus, Daria E. (2019) A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife, 8 . e41801. doi:10.7554/eLife.41801.001

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Official URL: http://dx.doi.org/10.7554/eLife.41801.001

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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.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Q Science > QR Microbiology
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Glycosylation, Macrophages, Metastasis, Drosophila melanogaster
Journal or Publication Title: eLife
Publisher: eLife Sciences Publications Ltd.
ISSN: 2050-084X
Official Date: 2019
Dates:
DateEvent
2019Published
26 March 2019Available
11 February 2019Accepted
7 February 2019Modified
Volume: 8
Article Number: e41801
DOI: 10.7554/eLife.41801.001
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
2P40OD010949-10A1 National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
P40OD018537National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
UNSPECIFIEDÖsterreichischen Akademie der WissenschaftenUNSPECIFIED
DASI_FWF01_P29638SAustrian Science Fundhttp://dx.doi.org/10.13039/501100002428
CIG 334077/IRTIMH2020 Marie Skłodowska-Curie Actionshttp://dx.doi.org/10.13039/100010665
GA-2012–32950 BB: DICH2020 Marie Skłodowska-Curie Actionshttp://dx.doi.org/10.13039/100010665
UNSPECIFIEDNÖ Forschungs- und Bildungsges.m.b.H. (NFB)http://viaf.org/viaf/184958581
665385H2020 European Research Councilhttp://dx.doi.org/10.13039/100010663
UNSPECIFIEDLundbeckfondenhttp://dx.doi.org/10.13039/501100003554
UNSPECIFIEDNovo Nordisk Fondenhttp://dx.doi.org/10.13039/501100009708
DNRF107Danmarks Grundforskningsfondhttp://dx.doi.org/10.13039/501100001732

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