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A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion

Katarína Valošková, Julia Biebl, Marko Roblek, Shamsi Emtenani, Attila Gyoergy, View ORCID ProfileMichaela Mišová, Aparna Ratheesh, Kateryna Shkarina, Ida S.B. Larsen, Sergey Y. Vakhrushev, Henrik Clausen, View ORCID ProfileDaria E. Siekhaus
doi: https://doi.org/10.1101/415547
Katarína Valošková
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Julia Biebl
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Marko Roblek
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Shamsi Emtenani
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Attila Gyoergy
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Michaela Mišová
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Michaela Mišová
Aparna Ratheesh
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Kateryna Shkarina
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
3University of Lausanne, Department of Biochemistry, Chemin des Boveresses 155-CP51-CH-1066 Epalinges, Switzerland
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Ida S.B. Larsen
2Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark
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Sergey Y. Vakhrushev
2Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark
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Henrik Clausen
2Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark
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Daria E. Siekhaus
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Daria E. Siekhaus
  • For correspondence: daria.siekhaus@ist.ac.at
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SUMMARY

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 protein pathways previously linked to cancer, most strongly on the protein sulfhydryl oxidase Qsox1 which we show is required for macrophage invasion. 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 12, 2018.
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A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion
Katarína Valošková, Julia Biebl, Marko Roblek, Shamsi Emtenani, Attila Gyoergy, Michaela Mišová, Aparna Ratheesh, Kateryna Shkarina, Ida S.B. Larsen, Sergey Y. Vakhrushev, Henrik Clausen, Daria E. Siekhaus
bioRxiv 415547; doi: https://doi.org/10.1101/415547
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A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion
Katarína Valošková, Julia Biebl, Marko Roblek, Shamsi Emtenani, Attila Gyoergy, Michaela Mišová, Aparna Ratheesh, Kateryna Shkarina, Ida S.B. Larsen, Sergey Y. Vakhrushev, Henrik Clausen, Daria E. Siekhaus
bioRxiv 415547; doi: https://doi.org/10.1101/415547

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