---
_id: '14274'
abstract:
- lang: eng
text: Immune responses rely on the rapid and coordinated migration of leukocytes.
Whereas it is well established that single-cell migration is often guided by gradients
of chemokines and other chemoattractants, it remains poorly understood how these
gradients are generated, maintained, and modulated. By combining experimental
data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor
(GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor
that steers migration, CCR7 also acts as a generator and a modulator of chemotactic
gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively
internalize the receptor and ligand as part of the canonical GPCR desensitization
response. We show that CCR7 internalization also acts as an effective sink for
the chemoattractant, dynamically shaping the spatiotemporal distribution of the
chemokine. This mechanism drives complex collective migration patterns, enabling
DCs to create or sharpen chemotactic gradients. We further show that these self-generated
gradients can sustain the long-range guidance of DCs, adapt collective migration
patterns to the size and geometry of the environment, and provide a guidance cue
for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses
and consumes its ligand can thus provide a novel mode of cellular self-organization.
acknowledgement: "We thank I. de Vries and the Scientific Service Units (Life Sciences,
Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute
of Science and Technology Austria for excellent support, as well as all the rotation
students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis
work was supported by grants from the European Research Council under the European
Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant
agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20)
to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research
Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U.
was supported by the European Union’s Horizon 2020 research and innovation programme
under the Marie Skłodowska-Curie grant agreement no. 754411."
article_number: adc9584
article_processing_charge: No
article_type: original
author:
- first_name: Jonna H
full_name: Alanko, Jonna H
id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
last_name: Alanko
orcid: 0000-0002-7698-3061
- first_name: Mehmet C
full_name: Ucar, Mehmet C
id: 50B2A802-6007-11E9-A42B-EB23E6697425
last_name: Ucar
orcid: 0000-0003-0506-4217
- first_name: Nikola
full_name: Canigova, Nikola
id: 3795523E-F248-11E8-B48F-1D18A9856A87
last_name: Canigova
orcid: 0000-0002-8518-5926
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink
for CCL19 to coordinate collective leukocyte migration. Science Immunology.
2023;8(87). doi:10.1126/sciimmunol.adc9584
apa: Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin,
J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate
collective leukocyte migration. Science Immunology. American Association
for the Advancement of Science. https://doi.org/10.1126/sciimmunol.adc9584
chicago: Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz,
Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor
and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Science
Immunology. American Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciimmunol.adc9584.
ieee: J. H. Alanko et al., “CCR7 acts as both a sensor and a sink for CCL19
to coordinate collective leukocyte migration,” Science Immunology, vol.
8, no. 87. American Association for the Advancement of Science, 2023.
ista: Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB,
Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective
leukocyte migration. Science Immunology. 8(87), adc9584.
mla: Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to
Coordinate Collective Leukocyte Migration.” Science Immunology, vol. 8,
no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:10.1126/sciimmunol.adc9584.
short: J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B.
Hannezo, M.K. Sixt, Science Immunology 8 (2023).
date_created: 2023-09-06T08:07:51Z
date_published: 2023-09-01T00:00:00Z
date_updated: 2023-12-21T14:30:01Z
day: '01'
department:
- _id: MiSi
- _id: EdHa
- _id: NanoFab
doi: 10.1126/sciimmunol.adc9584
ec_funded: 1
external_id:
isi:
- '001062110600003'
pmid:
- '37656776'
intvolume: ' 8'
isi: 1
issue: '87'
keyword:
- General Medicine
- Immunology
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1126/sciimmunol.adc9584
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 265E2996-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01250-B20
name: Nano-Analytics of Cellular Systems
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Science Immunology
publication_identifier:
issn:
- 2470-9468
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
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relation: research_data
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte
migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2023'
...
---
_id: '7420'
abstract:
- lang: eng
text: β1-integrins mediate cell–matrix interactions and their trafficking is important
in the dynamic regulation of cell adhesion, migration and malignant processes,
including cancer cell invasion. Here, we employ an RNAi screen to characterize
regulators of integrin traffic and identify the association of Golgi-localized
gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role
in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2
limits active β1-integrin levels in focal adhesions and decreases cancer cell
migration and invasion, which is in agreement with its ability to regulate the
dynamics of active integrins. By using the proximity-dependent biotin identification
(BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10,
as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular
accumulation of active β1-integrin, and reduces integrin activity in focal adhesions
and cell migration similarly to GGA2 depletion, indicating that both facilitate
active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are
important specificity determinants for integrin activity-dependent traffic.
article_number: jcs233387
article_processing_charge: No
article_type: original
author:
- first_name: Pranshu
full_name: Sahgal, Pranshu
last_name: Sahgal
- first_name: Jonna H
full_name: Alanko, Jonna H
id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
last_name: Alanko
orcid: 0000-0002-7698-3061
- first_name: Jaroslav
full_name: Icha, Jaroslav
last_name: Icha
- first_name: Ilkka
full_name: Paatero, Ilkka
last_name: Paatero
- first_name: Hellyeh
full_name: Hamidi, Hellyeh
last_name: Hamidi
- first_name: Antti
full_name: Arjonen, Antti
last_name: Arjonen
- first_name: Mika
full_name: Pietilä, Mika
last_name: Pietilä
- first_name: Anne
full_name: Rokka, Anne
last_name: Rokka
- first_name: Johanna
full_name: Ivaska, Johanna
last_name: Ivaska
citation:
ama: Sahgal P, Alanko JH, Icha J, et al. GGA2 and RAB13 promote activity-dependent
β1-integrin recycling. Journal of Cell Science. 2019;132(11). doi:10.1242/jcs.233387
apa: Sahgal, P., Alanko, J. H., Icha, J., Paatero, I., Hamidi, H., Arjonen, A.,
… Ivaska, J. (2019). GGA2 and RAB13 promote activity-dependent β1-integrin recycling.
Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.233387
chicago: Sahgal, Pranshu, Jonna H Alanko, Jaroslav Icha, Ilkka Paatero, Hellyeh
Hamidi, Antti Arjonen, Mika Pietilä, Anne Rokka, and Johanna Ivaska. “GGA2 and
RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” Journal of Cell Science.
The Company of Biologists, 2019. https://doi.org/10.1242/jcs.233387.
ieee: P. Sahgal et al., “GGA2 and RAB13 promote activity-dependent β1-integrin
recycling,” Journal of Cell Science, vol. 132, no. 11. The Company of Biologists,
2019.
ista: Sahgal P, Alanko JH, Icha J, Paatero I, Hamidi H, Arjonen A, Pietilä M, Rokka
A, Ivaska J. 2019. GGA2 and RAB13 promote activity-dependent β1-integrin recycling.
Journal of Cell Science. 132(11), jcs233387.
mla: Sahgal, Pranshu, et al. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin
Recycling.” Journal of Cell Science, vol. 132, no. 11, jcs233387, The Company
of Biologists, 2019, doi:10.1242/jcs.233387.
short: P. Sahgal, J.H. Alanko, J. Icha, I. Paatero, H. Hamidi, A. Arjonen, M. Pietilä,
A. Rokka, J. Ivaska, Journal of Cell Science 132 (2019).
date_created: 2020-01-30T10:31:42Z
date_published: 2019-06-07T00:00:00Z
date_updated: 2023-09-06T15:01:00Z
day: '07'
department:
- _id: MiSi
doi: 10.1242/jcs.233387
external_id:
isi:
- '000473327900017'
pmid:
- '31076515'
intvolume: ' 132'
isi: 1
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1242/jcs.233387
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
status: public
title: GGA2 and RAB13 promote activity-dependent β1-integrin recycling
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 132
year: '2019'
...
---
_id: '5861'
abstract:
- lang: eng
text: In zebrafish larvae, it is the cell type that determines how the cell responds
to a chemokine signal.
article_number: e37888
article_processing_charge: No
article_type: original
author:
- first_name: Jonna H
full_name: Alanko, Jonna H
id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
last_name: Alanko
orcid: 0000-0002-7698-3061
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Alanko JH, Sixt MK. The cell sets the tone. eLife. 2018;7. doi:10.7554/eLife.37888
apa: Alanko, J. H., & Sixt, M. K. (2018). The cell sets the tone. ELife.
eLife Sciences Publications. https://doi.org/10.7554/eLife.37888
chicago: Alanko, Jonna H, and Michael K Sixt. “The Cell Sets the Tone.” ELife.
eLife Sciences Publications, 2018. https://doi.org/10.7554/eLife.37888.
ieee: J. H. Alanko and M. K. Sixt, “The cell sets the tone,” eLife, vol.
7. eLife Sciences Publications, 2018.
ista: Alanko JH, Sixt MK. 2018. The cell sets the tone. eLife. 7, e37888.
mla: Alanko, Jonna H., and Michael K. Sixt. “The Cell Sets the Tone.” ELife,
vol. 7, e37888, eLife Sciences Publications, 2018, doi:10.7554/eLife.37888.
short: J.H. Alanko, M.K. Sixt, ELife 7 (2018).
date_created: 2019-01-20T22:59:19Z
date_published: 2018-06-06T00:00:00Z
date_updated: 2023-09-19T10:01:39Z
day: '06'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.7554/eLife.37888
external_id:
isi:
- '000434375000001'
file:
- access_level: open_access
checksum: f1c7ec2a809408d763c4b529a98f9a3b
content_type: application/pdf
creator: dernst
date_created: 2019-02-13T10:52:11Z
date_updated: 2020-07-14T12:47:13Z
file_id: '5973'
file_name: 2018_eLife_Alanko.pdf
file_size: 358141
relation: main_file
file_date_updated: 2020-07-14T12:47:13Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: The cell sets the tone
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: 7
year: '2018'
...