CLEC7A

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C-type lectin domain family 7, member A
Identifiers
Symbols CLEC7A ; BGR; CANDF4; CLECSF12; DECTIN1
External IDs OMIM606264 MGI1861431 HomoloGene49606 GeneCards: CLEC7A Gene
RNA expression pattern
PBB GE CLEC7A 221698 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 64581 56644
Ensembl ENSG00000172243 ENSMUSG00000079293
UniProt Q9BXN2 E9QPW2
RefSeq (mRNA) NM_022570.4 NM_020008.2
RefSeq (protein) NP_072092.2 NP_064392.2
Location (UCSC) Chr 12:
10.27 – 10.28 Mb
Chr 6:
129.41 – 129.42 Mb
PubMed search [1] [2]

C-type lectin domain family 7 member A/Dectin is a protein that in humans is encoded by the CLEC7A gene.[1]

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid Dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.[1]

Structure[edit]

Dectin-1 is a transmembrane protein containing an immunoreceptor tyrosine-based activation (ITAM)-like motif in its intracellular tail (which is involved in cellular activation) and single C-type lectin like domain (carbohydrate-recognition domain, CRD) in the extracellular region (which recognized ß-glucans and endogenous ligand on T cells). The CRD is separated from the membrane by a stalk region. CLEC7A contains putative N-linked sites of glycosylation in stalk region.[2][3]

Function[edit]

The C- type lectin receptors (CLRs) are class of signalling patogen recognition receptor (PRR) which are involved in antifungal immunity, but play important roles in immune response to other pathogens (bacteria, viruses and nematodes).[2]

CLEC7A express macrophages, neutrophils and dendritic cells.[4] Expression has also been studied on other immune cells including eosinophils and B cells.[5]

Dectin-1 recognize ß-glucans and carbohydrate found in fungal cell walls, some bacteria and plants and also can recognize other unidentified molecules (endogenous ligand on T-cells and ligand on mycobacteria).[2] Binding of ligand induce stimulation and mediates intracellular signalling via Dectin-1 ITAM-like motif. Recognition leads to induction of numerous cellular responses (respiratory burst, the production of arachidonic acid metabolites, DC maturation, ligand uptake by endocytosis and phagocytosis and induction of numerous cytokines and chemokines like TNF, IL-23, IL-6, IL-2).[6] CLEC7A can induce both Syk dependent or Syk independent pathways. Dimerization of Dectin-1 upon ligand binding lead to tyrosin phosphorylation by Src family kinases and to recruit Syk (spleen-tyrosine kinase) kinase. Syk activates transcription factor NFkB. This transcription factor is responsible for the production of numerous inflammatory cytokines. This receptor also triggers phagocytosis and production of reactive oxygen species (ROS).[5]

Antifungal immunity[edit]

CLEC7A has been shown to recognize species of several fungal genera, including Saccharomyces, Candida, Pneumocystis, Coccidioides, Penicillium and other. Recognition of these organism triggers many protective pathways, such as fungal uptake by phagocytosis and killing via respiratory burst. Activation signalization via Dectin-1 also triggers expression of many protecting antifungal cytokines/ chemokines (TNF, CXCL2, IL-1b, IL-1a, CCL3, GM-CSF, G-CSF and IL-6) and development of Th17.[6]

Costimulatory molecule[edit]

Dectin-1 can also operate as a costimulatory molecule via recognition of an endogenous ligand on T-cells. That lead to stimulation cellular activation and proliferation. CLEC7A can bind both CD4+ and CD8+ T cells.[6]

References[edit]

  1. ^ a b "Entrez Gene: CLEC7A C-type lectin domain family 7, member A". 
  2. ^ a b c Drummond RA, Brown GD (2011). "The role of Dectin-1 in the host defence against fungal infections.". Curr Opin Microbiol 14 (4): 392–9. doi:10.1016/j.mib.2011.07.001. PMID 21803640. 
  3. ^ Brown J, O'Callaghan CA, Marshall AS, Gilbert RJ, Siebold C, Gordon S et al. (2007). "Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function.". Protein Sci 16 (6): 1042–52. doi:10.1110/ps.072791207. PMC 2206667. PMID 17473009. 
  4. ^ Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L, Gordon S et al. (2002). "The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages.". J Immunol 169 (7): 3876–82. PMID 12244185. 
  5. ^ a b Saijo S, Iwakura Y (2011). "Dectin-1 and Dectin-2 in innate immunity against fungi.". Int Immunol 23 (8): 467–72. doi:10.1093/intimm/dxr046. PMID 21677049. 
  6. ^ a b c Huysamen C, Brown GD (2009). "The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors.". FEMS Microbiol Lett 290 (2): 121–8. doi:10.1111/j.1574-6968.2008.01418.x. PMC 2704933. PMID 19025564. 

Further reading[edit]