Information transfer in mammalian glycan-based communication
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.
-
Data from: Information transfer in mammalian glycan-based communicationDryad Digital Repository, doi:10.5061/dryad.tx95x69xq.
Article and author information
Author details
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.
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.
Metrics
-
- 1,538
- views
-
- 275
- downloads
-
- 6
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cell Biology
- Evolutionary Biology
Maintenance of rod-shape in bacterial cells depends on the actin-like protein MreB. Deletion of mreB from Pseudomonas fluorescens SBW25 results in viable spherical cells of variable volume and reduced fitness. Using a combination of time-resolved microscopy and biochemical assay of peptidoglycan synthesis, we show that reduced fitness is a consequence of perturbed cell size homeostasis that arises primarily from differential growth of daughter cells. A 1000-generation selection experiment resulted in rapid restoration of fitness with derived cells retaining spherical shape. Mutations in the peptidoglycan synthesis protein Pbp1A were identified as the main route for evolutionary rescue with genetic reconstructions demonstrating causality. Compensatory pbp1A mutations that targeted transpeptidase activity enhanced homogeneity of cell wall synthesis on lateral surfaces and restored cell size homeostasis. Mechanistic explanations require enhanced understanding of why deletion of mreB causes heterogeneity in cell wall synthesis. We conclude by presenting two testable hypotheses, one of which posits that heterogeneity stems from non-functional cell wall synthesis machinery, while the second posits that the machinery is functional, albeit stalled. Overall, our data provide support for the second hypothesis and draw attention to the importance of balance between transpeptidase and glycosyltransferase functions of peptidoglycan building enzymes for cell shape determination.
-
- Cell Biology
- Developmental Biology
Mechanical forces play a critical role in tendon development and function, influencing cell behavior through mechanotransduction signaling pathways and subsequent extracellular matrix (ECM) remodeling. Here we investigate the molecular mechanisms by which tenocytes in developing zebrafish embryos respond to muscle contraction forces during the onset of swimming and cranial muscle activity. Using genome-wide bulk RNA sequencing of FAC-sorted tenocytes we identify novel tenocyte markers and genes involved in tendon mechanotransduction. Embryonic tendons show dramatic changes in expression of matrix remodeling associated 5b (mxra5b), matrilin1 (matn1), and the transcription factor kruppel-like factor 2a (klf2a), as muscles start to contract. Using embryos paralyzed either by loss of muscle contractility or neuromuscular stimulation we confirm that muscle contractile forces influence the spatial and temporal expression patterns of all three genes. Quantification of these gene expression changes across tenocytes at multiple tendon entheses and myotendinous junctions reveals that their responses depend on force intensity, duration and tissue stiffness. These force-dependent feedback mechanisms in tendons, particularly in the ECM, have important implications for improved treatments of tendon injuries and atrophy.