[{"title":"CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration","oa_version":"Published Version","author":[{"last_name":"Alanko","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","full_name":"Alanko, Jonna H","first_name":"Jonna H","orcid":"0000-0002-7698-3061"},{"last_name":"Ucar","full_name":"Ucar, Mehmet C","id":"50B2A802-6007-11E9-A42B-EB23E6697425","orcid":"0000-0003-0506-4217","first_name":"Mehmet C"},{"orcid":"0000-0002-8518-5926","first_name":"Nikola","last_name":"Canigova","full_name":"Canigova, Nikola","id":"3795523E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julian A","full_name":"Stopp, Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","last_name":"Stopp"},{"last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","first_name":"Jan"},{"orcid":"0000-0001-5145-4609","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","full_name":"Merrin, Jack","last_name":"Merrin"},{"first_name":"Edouard B","orcid":"0000-0001-6005-1561","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt"}],"day":"01","scopus_import":"1","article_type":"original","date_created":"2023-09-06T08:07:51Z","volume":8,"intvolume":"         8","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."}],"publication_status":"published","publication_identifier":{"issn":["2470-9468"]},"month":"09","article_number":"adc9584","department":[{"_id":"MiSi"},{"_id":"EdHa"},{"_id":"NanoFab"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"87","citation":{"mla":"Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>.","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. <i>Science Immunology</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>","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.","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.” <i>Science Immunology</i>. American Association for the Advancement of Science, 2023. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>.","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).","ieee":"J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol. 8, no. 87. American Association for the Advancement of Science, 2023.","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. <i>Science Immunology</i>. 2023;8(87). doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>"},"publisher":"American Association for the Advancement of Science","doi":"10.1126/sciimmunol.adc9584","article_processing_charge":"No","type":"journal_article","date_updated":"2023-12-21T14:30:01Z","_id":"14274","quality_controlled":"1","main_file_link":[{"url":"https://doi.org/10.1126/sciimmunol.adc9584","open_access":"1"}],"external_id":{"pmid":["37656776"],"isi":["001062110600003"]},"related_material":{"record":[{"relation":"research_data","status":"public","id":"14279"},{"status":"public","relation":"dissertation_contains","id":"14697"}]},"year":"2023","isi":1,"keyword":["General Medicine","Immunology"],"project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"851288","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E"},{"_id":"265E2996-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Nano-Analytics of Cellular Systems","grant_number":"W01250-B20"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"status":"public","publication":"Science Immunology","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.","date_published":"2023-09-01T00:00:00Z","pmid":1,"ec_funded":1},{"doi":"10.1242/jcs.233387","article_processing_charge":"No","publisher":"The Company of Biologists","date_updated":"2023-09-06T15:01:00Z","_id":"7420","type":"journal_article","main_file_link":[{"url":"https://doi.org/10.1242/jcs.233387","open_access":"1"}],"quality_controlled":"1","year":"2019","isi":1,"external_id":{"isi":["000473327900017"],"pmid":["31076515"]},"publication":"Journal of Cell Science","status":"public","pmid":1,"date_published":"2019-06-07T00:00:00Z","author":[{"last_name":"Sahgal","full_name":"Sahgal, Pranshu","first_name":"Pranshu"},{"last_name":"Alanko","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","full_name":"Alanko, Jonna H","first_name":"Jonna H","orcid":"0000-0002-7698-3061"},{"first_name":"Jaroslav","last_name":"Icha","full_name":"Icha, Jaroslav"},{"first_name":"Ilkka","full_name":"Paatero, Ilkka","last_name":"Paatero"},{"last_name":"Hamidi","full_name":"Hamidi, Hellyeh","first_name":"Hellyeh"},{"first_name":"Antti","full_name":"Arjonen, Antti","last_name":"Arjonen"},{"last_name":"Pietilä","full_name":"Pietilä, Mika","first_name":"Mika"},{"full_name":"Rokka, Anne","last_name":"Rokka","first_name":"Anne"},{"full_name":"Ivaska, Johanna","last_name":"Ivaska","first_name":"Johanna"}],"day":"07","title":"GGA2 and RAB13 promote activity-dependent β1-integrin recycling","oa_version":"Published Version","volume":132,"article_type":"original","date_created":"2020-01-30T10:31:42Z","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."}],"intvolume":"       132","publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"publication_status":"published","month":"06","department":[{"_id":"MiSi"}],"article_number":"jcs233387","oa":1,"language":[{"iso":"eng"}],"issue":"11","citation":{"ieee":"P. Sahgal <i>et al.</i>, “GGA2 and RAB13 promote activity-dependent β1-integrin recycling,” <i>Journal of Cell Science</i>, vol. 132, no. 11. The Company of Biologists, 2019.","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).","ama":"Sahgal P, Alanko JH, Icha J, et al. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. <i>Journal of Cell Science</i>. 2019;132(11). doi:<a href=\"https://doi.org/10.1242/jcs.233387\">10.1242/jcs.233387</a>","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. <i>Journal of Cell Science</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/jcs.233387\">https://doi.org/10.1242/jcs.233387</a>","mla":"Sahgal, Pranshu, et al. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” <i>Journal of Cell Science</i>, vol. 132, no. 11, jcs233387, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/jcs.233387\">10.1242/jcs.233387</a>.","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.” <i>Journal of Cell Science</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/jcs.233387\">https://doi.org/10.1242/jcs.233387</a>.","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."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"},{"isi":1,"year":"2018","external_id":{"isi":["000434375000001"]},"date_published":"2018-06-06T00:00:00Z","publication":"eLife","status":"public","date_updated":"2023-09-19T10:01:39Z","_id":"5861","type":"journal_article","doi":"10.7554/eLife.37888","article_processing_charge":"No","publisher":"eLife Sciences Publications","quality_controlled":"1","ddc":["570"],"department":[{"_id":"MiSi"}],"article_number":"e37888","file":[{"checksum":"f1c7ec2a809408d763c4b529a98f9a3b","relation":"main_file","content_type":"application/pdf","access_level":"open_access","file_name":"2018_eLife_Alanko.pdf","file_id":"5973","creator":"dernst","date_updated":"2020-07-14T12:47:13Z","date_created":"2019-02-13T10:52:11Z","file_size":358141}],"month":"06","citation":{"ama":"Alanko JH, Sixt MK. The cell sets the tone. <i>eLife</i>. 2018;7. doi:<a href=\"https://doi.org/10.7554/eLife.37888\">10.7554/eLife.37888</a>","short":"J.H. Alanko, M.K. Sixt, ELife 7 (2018).","ieee":"J. H. Alanko and M. K. Sixt, “The cell sets the tone,” <i>eLife</i>, vol. 7. eLife Sciences Publications, 2018.","ista":"Alanko JH, Sixt MK. 2018. The cell sets the tone. eLife. 7, e37888.","chicago":"Alanko, Jonna H, and Michael K Sixt. “The Cell Sets the Tone.” <i>ELife</i>. eLife Sciences Publications, 2018. <a href=\"https://doi.org/10.7554/eLife.37888\">https://doi.org/10.7554/eLife.37888</a>.","mla":"Alanko, Jonna H., and Michael K. Sixt. “The Cell Sets the Tone.” <i>ELife</i>, vol. 7, e37888, eLife Sciences Publications, 2018, doi:<a href=\"https://doi.org/10.7554/eLife.37888\">10.7554/eLife.37888</a>.","apa":"Alanko, J. H., &#38; Sixt, M. K. (2018). The cell sets the tone. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.37888\">https://doi.org/10.7554/eLife.37888</a>"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"language":[{"iso":"eng"}],"volume":7,"article_type":"original","date_created":"2019-01-20T22:59:19Z","author":[{"id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","full_name":"Alanko, Jonna H","last_name":"Alanko","orcid":"0000-0002-7698-3061","first_name":"Jonna H"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179","first_name":"Michael K"}],"scopus_import":"1","day":"06","title":"The cell sets the tone","oa_version":"Published Version","publication_status":"published","publication_identifier":{"issn":["2050084X"]},"file_date_updated":"2020-07-14T12:47:13Z","has_accepted_license":"1","license":"https://creativecommons.org/licenses/by/4.0/","abstract":[{"text":"In zebrafish larvae, it is the cell type that determines how the cell responds to a chemokine signal.","lang":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"         7"}]