Schwarz, Jan, Bierbaum, Veronika, Vaahtomeri, Kari, Hauschild, Robert, Brown, Markus, de Vries, Ingrid, Leithner, Alexander ORCID: 0000-0002-1073-744X, Reversat, Anne ORCID: 0000-0003-0666-8928, Merrin, Jack, Tarrant, Teresa, Bollenbach, Tobias ORCID: 0000-0003-4398-476X and Sixt, Michael (2017). Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal-to-Noise Ratio and Dependent on GRK6. Curr. Biol., 27 (9). S. 1314 - 1326. CAMBRIDGE: CELL PRESS. ISSN 1879-0445

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Abstract

Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable roads'' ensure optimal guidance in vivo.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schwarz, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bierbaum, VeronikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vaahtomeri, KariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauschild, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brown, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries, IngridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leithner, AlexanderUNSPECIFIEDorcid.org/0000-0002-1073-744XUNSPECIFIED
Reversat, AnneUNSPECIFIEDorcid.org/0000-0003-0666-8928UNSPECIFIED
Merrin, JackUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarrant, TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bollenbach, TobiasUNSPECIFIEDorcid.org/0000-0003-4398-476XUNSPECIFIED
Sixt, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-231303
DOI: 10.1016/j.cub.2017.04.004
Journal or Publication Title: Curr. Biol.
Volume: 27
Number: 9
Page Range: S. 1314 - 1326
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1879-0445
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COUPLED RECEPTOR KINASES; EUKARYOTIC CHEMOTAXIS; LEUKOCYTE MIGRATION; LIGANDS; CCL21; MOTILITY; CCL19; DESENSITIZATION; RECRUITMENT; ACTIVATIONMultiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23130

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