---
_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'
...