Information transfer in mammalian glycan-based communication.
Felix F FuchsbergerDongyoon KimNatalia BaranovaHanka VrbanMarten KagelmacherRobert WawrzinekChristoph RademacherPublished in: eLife (2023)
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.
Keyphrases
- single cell
- health information
- cell surface
- signaling pathway
- rna seq
- healthcare
- magnetic resonance
- inflammatory response
- stem cells
- magnetic resonance imaging
- dendritic cells
- toll like receptor
- cell therapy
- social media
- attention deficit hyperactivity disorder
- machine learning
- big data
- cystic fibrosis
- staphylococcus aureus
- transcription factor
- lps induced
- autism spectrum disorder
- long non coding rna
- biofilm formation