--- _id: '6187' abstract: - lang: eng text: 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. acknowledged_ssus: - _id: LifeSc article_number: e41801 article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková - first_name: Julia full_name: Biebl, Julia id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87 last_name: Biebl - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Michaela full_name: Misova, Michaela id: 495A3C32-F248-11E8-B48F-1D18A9856A87 last_name: Misova orcid: 0000-0003-2427-6856 - first_name: Aparna full_name: Ratheesh, Aparna id: 2F064CFE-F248-11E8-B48F-1D18A9856A87 last_name: Ratheesh orcid: 0000-0001-7190-0776 - first_name: Patricia full_name: Rodrigues, Patricia id: 2CE4065A-F248-11E8-B48F-1D18A9856A87 last_name: Rodrigues - first_name: Katerina full_name: Shkarina, Katerina last_name: Shkarina - first_name: Ida Signe Bohse full_name: Larsen, Ida Signe Bohse last_name: Larsen - first_name: Sergey Y full_name: Vakhrushev, Sergey Y last_name: Vakhrushev - first_name: Henrik full_name: Clausen, Henrik last_name: Clausen - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: ama: Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 2019;8. doi:10.7554/elife.41801 apa: Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M., … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.41801 chicago: Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801. ieee: K. Valosková et al., “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801. mla: Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife, vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801. short: K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A. Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen, D.E. Siekhaus, ELife 8 (2019). date_created: 2019-03-28T13:37:45Z date_published: 2019-03-26T00:00:00Z date_updated: 2024-03-28T23:30:30Z day: '26' ddc: - '570' department: - _id: DaSi doi: 10.7554/elife.41801 ec_funded: 1 external_id: isi: - '000462530200001' file: - access_level: open_access checksum: cc0d1a512559d52e7e7cb0e9b9854b40 content_type: application/pdf creator: dernst date_created: 2019-03-28T14:00:41Z date_updated: 2020-07-14T12:47:23Z file_id: '6188' file_name: 2019_eLife_Valoskova.pdf file_size: 4496017 relation: main_file file_date_updated: 2020-07-14T12:47:23Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '03' oa: 1 oa_version: Published Version project: - _id: 253CDE40-B435-11E9-9278-68D0E5697425 grant_number: '24283' name: Examination of the role of a MFS transporter in the migration of Drosophila immune cells - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: The role of Drosophila TNF alpha in immune cell invasion - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 25388084-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '329540' name: 'Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/ record: - id: '6530' relation: dissertation_contains - id: '8983' relation: dissertation_contains status: public - id: '6546' relation: dissertation_contains status: public scopus_import: '1' status: public title: A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2019' ... --- _id: '6546' abstract: - lang: eng text: "Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant 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 \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n" acknowledged_ssus: - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková citation: ama: Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546 apa: Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546 chicago: Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546. ieee: K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019. ista: Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. mla: Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546. short: K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-06-07T12:49:19Z date_published: 2019-06-07T00:00:00Z date_updated: 2023-09-19T10:15:54Z day: '07' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:6546 file: - access_level: closed checksum: 68949c2d96210b45b981a23e9c9cd93c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: khribikova date_created: 2019-06-07T13:00:04Z date_updated: 2020-07-14T12:47:33Z embargo_to: open_access file_id: '6549' file_name: Katarina Valoskova_PhD thesis_final version.docx file_size: 14110626 relation: source_file - access_level: open_access checksum: 555329cd76e196c96f5278c480ee2e6e content_type: application/pdf creator: khribikova date_created: 2019-06-07T13:00:08Z date_updated: 2021-02-11T11:17:14Z embargo: 2020-06-07 file_id: '6550' file_name: Katarina Valoskova_PhD thesis_final version.pdf file_size: 10054156 relation: main_file file_date_updated: 2021-02-11T11:17:14Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '141' project: - _id: 253CDE40-B435-11E9-9278-68D0E5697425 grant_number: '24283' name: Examination of the role of a MFS transporter in the migration of Drosophila immune cells publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6187' relation: part_of_dissertation status: public - id: '544' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '544' abstract: - lang: eng text: Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult. acknowledged_ssus: - _id: LifeSc acknowledgement: ' A. Ratheesh also by Marie Curie IIF GA-2012-32950BB:DICJI, Marko Roblek by the provincial government of Lower Austria, K. Valoskova and S. Wachner by DOC Fellowships from the Austrian Academy of Sciences, ' article_processing_charge: No author: - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Aparna full_name: Ratheesh, Aparna id: 2F064CFE-F248-11E8-B48F-1D18A9856A87 last_name: Ratheesh orcid: 0000-0001-7190-0776 - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková - first_name: Vera full_name: Belyaeva, Vera id: 47F080FE-F248-11E8-B48F-1D18A9856A87 last_name: Belyaeva - first_name: Stephanie full_name: Wachner, Stephanie id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87 last_name: Wachner - first_name: Yutaka full_name: Matsubayashi, Yutaka last_name: Matsubayashi - first_name: Besaiz full_name: Sanchez Sanchez, Besaiz last_name: Sanchez Sanchez - first_name: Brian full_name: Stramer, Brian last_name: Stramer - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: ama: 'György A, Roblek M, Ratheesh A, et al. Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. 2018;8(3):845-857. doi:10.1534/g3.117.300452' apa: 'György, A., Roblek, M., Ratheesh, A., Valosková, K., Belyaeva, V., Wachner, S., … Siekhaus, D. E. (2018). Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. Genetics Society of America. https://doi.org/10.1534/g3.117.300452' chicago: 'György, Attila, Marko Roblek, Aparna Ratheesh, Katarina Valosková, Vera Belyaeva, Stephanie Wachner, Yutaka Matsubayashi, Besaiz Sanchez Sanchez, Brian Stramer, and Daria E Siekhaus. “Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.” G3: Genes, Genomes, Genetics. Genetics Society of America, 2018. https://doi.org/10.1534/g3.117.300452.' ieee: 'A. György et al., “Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues,” G3: Genes, Genomes, Genetics, vol. 8, no. 3. Genetics Society of America, pp. 845–857, 2018.' ista: 'György A, Roblek M, Ratheesh A, Valosková K, Belyaeva V, Wachner S, Matsubayashi Y, Sanchez Sanchez B, Stramer B, Siekhaus DE. 2018. Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. 8(3), 845–857.' mla: 'György, Attila, et al. “Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.” G3: Genes, Genomes, Genetics, vol. 8, no. 3, Genetics Society of America, 2018, pp. 845–57, doi:10.1534/g3.117.300452.' short: 'A. György, M. Roblek, A. Ratheesh, K. Valosková, V. Belyaeva, S. Wachner, Y. Matsubayashi, B. Sanchez Sanchez, B. Stramer, D.E. Siekhaus, G3: Genes, Genomes, Genetics 8 (2018) 845–857.' date_created: 2018-12-11T11:47:05Z date_published: 2018-03-01T00:00:00Z date_updated: 2024-03-28T23:30:30Z day: '01' ddc: - '570' department: - _id: DaSi doi: 10.1534/g3.117.300452 ec_funded: 1 external_id: isi: - '000426693300011' file: - access_level: open_access checksum: 7d9d28b915159078a4ca7add568010e8 content_type: application/pdf creator: system date_created: 2018-12-12T10:11:48Z date_updated: 2020-07-14T12:46:56Z file_id: '4905' file_name: IST-2018-990-v1+1_2018_Gyoergy_Tools_allowing.pdf file_size: 2251222 relation: main_file file_date_updated: 2020-07-14T12:46:56Z has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 845 - 857 project: - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: Drosophila TNFa´s Funktion in Immunzellen - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: The role of Drosophila TNF alpha in immune cell invasion - _id: 2637E9C0-B435-11E9-9278-68D0E5697425 grant_number: 'LSC16-021 ' name: Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions publication: 'G3: Genes, Genomes, Genetics' publication_status: published publisher: Genetics Society of America publist_id: '7271' pubrep_id: '990' quality_controlled: '1' related_material: record: - id: '6530' relation: research_paper - id: '6543' relation: research_paper - id: '11193' relation: dissertation_contains status: public - id: '6546' relation: dissertation_contains status: public scopus_import: '1' status: public title: Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 8 year: '2018' ...