Information transfer in mammalian glycan-based communication
- University of Vienna, Austria
- Max Planck Institute of Colloids and Interfaces, Germany
Abstract
Glycan-binding proteins, so-called lectins, are exposed on mammalian cell surfaces and decipher the information encoded within glycans translating it into biochemical signal transduction pathways in the cell. These glycan-lectin communication pathways are complex and difficult to analyze. However, quantitative data with single cell resolution provide means to disentangle the associated signaling cascades. We chose C-type lectin receptors (CTLs) expressed on immune cells as a model system to study their capacity to transmit information encoded in glycans of incoming particles. In particular, we used NF-κB-reporter cell lines expressing DC-SIGN, MCL, dectin-1, dectin-2, and mincle, as well as TNFαR and TLR-1&2 in monocytic cell lines and compared their transmission of glycan-encoded information. All receptors did transmit information with similar signaling capacity, except dectin-2. This lectin was identified to less efficient in information transmission compared to the other CTLs and even while the sensitivity of the dectin-2 pathway was enhanced by overexpression of its co-receptor FcRγ, its transmitted information was not. Next, we expanded our investigation towards the integration of multiple signal transduction pathways including synergistic lectins, which is crucial during pathogen recognition. We show how the signaling capacity of lectin receptors using a similar signal transduction pathway (dectin-1 and dectin-2) are being integrated by compromising between the lectins. In contrast, co-expression of MCL synergistically enhanced the dectin-2 signaling capacity, particularly at low glycan stimulant concentration. By using dectin-2 and other lectins as examples, we demonstrate how signaling capacity of dectin-2 is modulated in the presence of other lectins and therefore the findings provide insight into how immune cells translate glycan information using multivalent interactions.
Data availability
We have uploaded the raw data of the study to Dryad and updated it during the revision process. https://doi.org/10.5061/dryad.tx95x69xqOur scripts for data evaluation are also linked to GitHub and stated in the manuscript.
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Data from: Information transfer in mammalian glycan-based communicationDryad Digital Repository, doi:10.5061/dryad.tx95x69xq.
Article and author information
Author details
Christoph Rademacher
Funding
European Research Council (716024)
- Marten Kagelmacher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andre Levchenko, Yale University, United States
Version history
- Received: April 14, 2021
- Preprint posted: May 10, 2021 (view preprint)
- Accepted: February 19, 2023
- Accepted Manuscript published: February 20, 2023 (version 1)
- Version of Record published: March 14, 2023 (version 2)
- Version of Record updated: March 31, 2023 (version 3)
Copyright
© 2023, Fuchsberger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Information transfer in mammalian glycan-based communication
eLife 12:e69415.
https://doi.org/10.7554/eLife.69415
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