Ligand binding and signaling of dendritic cell immunoreceptor (DCIR) is modulated by the glycosylation of the carbohydrate recognition domain

C-type lectins are innate receptors expressed on antigen-presenting cells that are involved in the recognition of glycosylated pathogens and self-glycoproteins. Upon ligand binding, internalization and/or signaling often occur. Little is known on the glycan specificity and ligands of the Dendritic C...

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Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e66266-e66266
Main Authors: Bloem, Karien, Vuist, Ilona M, van der Plas, Arend-Jan, Knippels, Léon M J, Garssen, Johan, García-Vallejo, Juan J, van Vliet, Sandra J, van Kooyk, Yvette
Format: Article
Language:English
Subjects:
Animals
Antigen-presenting cells
Arthritis
Binding
Biology
Blotting, Western
Carbohydrates
CHO Cells
Cricetulus
Dendritic cells
Flow Cytometry
Glycan
Glycoproteins
Glycosylation
Humans
Immunology
Immunoprecipitation
Immunoreceptor tyrosine-based inhibition motif
Internalization
Lectins
Lectins, C-Type - chemistry
Lectins, C-Type - metabolism
Ligands
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - metabolism
Nutrition
Pharmaceutical sciences
Phosphatase
Phosphorylation
Polysaccharides
Polysaccharides - metabolism
Protein Binding
Proteins
Receptors
Receptors, Immunologic - chemistry
Receptors, Immunologic - metabolism
Recognition
Signal Transduction
Signaling
Tyrosine
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Summary:C-type lectins are innate receptors expressed on antigen-presenting cells that are involved in the recognition of glycosylated pathogens and self-glycoproteins. Upon ligand binding, internalization and/or signaling often occur. Little is known on the glycan specificity and ligands of the Dendritic Cell Immunoreceptor (DCIR), the only classical C-type lectin that contains an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM). Here we show that purified DCIR binds the glycan structures Lewis(b) and Man3. Interestingly, binding could not be detected when DCIR was expressed on cells. Since DCIR has an N-glycosylation site inside its carbohydrate recognition domain (CRD), we investigated the effect of this glycan in ligand recognition. Removing or truncating the glycans present on purified DCIR increased the affinity for DCIR-binding glycans. Nevertheless, altering the glycosylation status of the DCIR expressing cell or mutating the N-glycosylation site of DCIR itself did not increase glycan binding. In contrast, cis and trans interactions with glycans induced DCIR mediated signaling, resulting in a decreased phosphorylation of the ITIM sequence. These results show that glycan binding to DCIR is influenced by the glycosylation of the CRD region in DCIR and that interaction with its ligands result in signaling via its ITIM motif.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066266