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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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WRAP-major-facilitator-superfamily-orchestrates-O-glycosylation-macrophage-invasion-Ratheesh-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4Mb) | Preview |
Official URL: http://dx.doi.org/10.7554/eLife.41801.001
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 | ||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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| 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 |
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| 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: |
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| 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: |
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