CLEC10A
C-type lectin domain family 10 member A (CLEC10A) also designated as CD301 is a protein that in humans is encoded by the CLEC10A gene.[5] CLEC10A is part of the C-type lectin superfamily and binds to N-Acetylgalactosamine (GalNAc). It is mainly expressed on myeloid cells and also on oocytes and very early stages of embryogenesis. CLEC10A is used as a marker of the CD1c+ dendritic cell subgroup, also called cDC2.[6] The actions of CLEC10A are diverse, depending on the ligand and environment.[7]
| CLEC10A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | CLEC10A, CD301, CLECSF13, CLECSF14, HML, HML2, MGL, C-type lectin domain family 10 member A, C-type lectin domain containing 10A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 605999 MGI: 96975 HomoloGene: 7836 GeneCards: CLEC10A | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Function
Generally, C-type lectins bind carbohydrate moieties usually in the presence of Ca2+ and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response.[8]
CLEC10A is a type II transmembrane protein (passing one time through the membrane and oriented with the N terminus inward) that induces endocytosis after ligand binding. To release the ligand in the endosome, participating Ca2+ ions have to be unbound first. This leads to a significant increase in cytoplasmic Ca2+ concentration.[7]
CLEC10A binds most strongly to N-Acetylgalactosamine (GalNAc), preferring α-GalNAc over β-GalNAc, unmodified galactose is bound very weakly.[7] CLEC10A is the only C-type lectin within the human immune system that exclusively recognizes terminal GalNAc.[9] This includes the Tn antigen (GalNAc O-bound to serine or threonine) which is prominently expressed on carcinomas, where it can also be sialylated. These tumor-associated antigens (Neu5Acα2,6-Tn, and NeuGcα2,6-Tn) are also bound.[10]
CLEC10A has also been shown to bind GalNAc in the teichoic acid of the Staphylococcus aureus cell wall and the surface of parasites.[11][12]
CLEC10A is expressed by dendritic cells that differentiate from monocytes recruited to inflammatory environments.[13]
CD45 contains a Tn antigen in exon B. CD45 has 3 important exons (4,5,6), that are designated A,B,C. Isoforms of CD45 are labeled depending on the presence of these exons. CLEC10A can for example bind CD45RB or CD45R, which is shorthand for CD45RABC. Binding causes attenuation of T cell activity, apoptosis, and immunosuppression. However, active T cells express shorter isoforms of CD45 (CD45RO, CD45RA) that lack exon B.[7]
CLEC10A signalling induces IL-10 production in dendritic cells, in part through increasing intracellular Ca2+ concentration. IL-10 is the main regulatory and anti-inflammatory cytokine produced in humans. In contrast, low concentrations of intracellular Ca2+ result in production of IL-12, a pro-inflammatory cytokine that also leads to Th1 polarisation.[7]
In cancer research, CLEC10A expression was found to both improve[14][15][16] and worsen[17] survival.
In animal models, deficiency of the orthologue to CLEC10A, Mgl1 is associated with worse outcomes in infection and excessive inflammation.[18]
References
- GRCh38: Ensembl release 89: ENSG00000132514 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000000318 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Suzuki N, Yamamoto K, Toyoshima S, Osawa T, Irimura T (January 1996). "Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen". Journal of Immunology. 156 (1): 128–135. doi:10.4049/jimmunol.156.1.128. PMID 8598452. S2CID 25597354.
- Heger L, Balk S, Lühr JJ, Heidkamp GF, Lehmann CH, Hatscher L, et al. (2018-04-27). "CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion". Frontiers in Immunology. 9: 744. doi:10.3389/fimmu.2018.00744. PMC 5934495. PMID 29755453.
- Hoober JK (July 2020). "ASGR1 and Its Enigmatic Relative, CLEC10A". International Journal of Molecular Sciences. 21 (14): 4818. doi:10.3390/ijms21144818. PMC 7404283. PMID 32650396.
- Zelensky AN, Gready JE (December 2005). "The C-type lectin-like domain superfamily". The FEBS Journal. 272 (24): 6179–6217. doi:10.1111/j.1742-4658.2005.05031.x. PMID 16336259. S2CID 7084402.
- van Kooyk Y, Ilarregui JM, van Vliet SJ (February 2015). "Novel insights into the immunomodulatory role of the dendritic cell and macrophage-expressed C-type lectin MGL". Immunobiology. 220 (2): 185–192. doi:10.1016/j.imbio.2014.10.002. PMID 25454488.
- Mortezai N, Behnken HN, Kurze AK, Ludewig P, Buck F, Meyer B, Wagener C (July 2013). "Tumor-associated Neu5Ac-Tn and Neu5Gc-Tn antigens bind to C-type lectin CLEC10A (CD301, MGL)". Glycobiology. 23 (7): 844–852. doi:10.1093/glycob/cwt021. PMID 23507963.
- Mnich ME, van Dalen R, Gerlach D, Hendriks A, Xia G, Peschel A, et al. (October 2019). "The C-type lectin receptor MGL senses N-acetylgalactosamine on the unique Staphylococcus aureus ST395 wall teichoic acid". Cellular Microbiology. 21 (10): e13072. doi:10.1111/cmi.13072. PMC 6771913. PMID 31219660.
- van Vliet SJ, van Liempt E, Saeland E, Aarnoudse CA, Appelmelk B, Irimura T, et al. (May 2005). "Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells". International Immunology. 17 (5): 661–669. doi:10.1093/intimm/dxh246. PMID 15802303.
- Tang-Huau TL, Gueguen P, Goudot C, Durand M, Bohec M, Baulande S, et al. (July 2018). "Human in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway". Nature Communications. 9 (1): 2570. Bibcode:2018NatCo...9.2570T. doi:10.1038/s41467-018-04985-0. PMC 6028641. PMID 29967419.
- Kurze AK, Buhs S, Eggert D, Oliveira-Ferrer L, Müller V, Niendorf A, et al. (August 2019). "Immature O-glycans recognized by the macrophage glycoreceptor CLEC10A (MGL) are induced by 4-hydroxy-tamoxifen, oxidative stress and DNA-damage in breast cancer cells". Cell Communication and Signaling. 17 (1): 107. doi:10.1186/s12964-019-0420-9. PMC 6712659. PMID 31455323.
- Eggink LL, Roby KF, Cote R, Kenneth Hoober J (April 2018). "An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides". Journal for Immunotherapy of Cancer. 6 (1): 28. doi:10.1186/s40425-018-0339-5. PMC 5905120. PMID 29665849.
- Qin Y, Wang L, Zhang L, Li J, Liao L, Huang L, et al. (2021). "Immunological role and prognostic potential of CLEC10A in pan-cancer". American Journal of Translational Research. 14 (5): 2844–2860. doi:10.2139/ssrn.3932103. PMC 9185031. PMID 35702069. S2CID 242193292.
- Dusoswa SA, Verhoeff J, Abels E, Méndez-Huergo SP, Croci DO, Kuijper LH, et al. (February 2020). "Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin". Proceedings of the National Academy of Sciences of the United States of America. 117 (7): 3693–3703. Bibcode:2020PNAS..117.3693D. doi:10.1073/pnas.1907921117. PMC 7035608. PMID 32019882.
- Jondle CN, Sharma A, Simonson TJ, Larson B, Mishra BB, Sharma J (April 2016). "Macrophage Galactose-Type Lectin-1 Deficiency Is Associated with Increased Neutrophilia and Hyperinflammation in Gram-Negative Pneumonia". Journal of Immunology. 196 (7): 3088–3096. doi:10.4049/jimmunol.1501790. PMC 4936400. PMID 26912318.
External links
- Human CLEC10A genome location and CLEC10A gene details page in the UCSC Genome Browser.
Further reading
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- van Vliet SJ, Steeghs L, Bruijns SC, Vaezirad MM, Snijders Blok C, Arenas Busto JA, et al. (October 2009). Seifert HS (ed.). "Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses". PLOS Pathogens. 5 (10): e1000625. doi:10.1371/journal.ppat.1000625. PMC 2757725. PMID 19834553.
- Iijima M, Tomita M, Morozumi S, Kawagashira Y, Nakamura T, Koike H, et al. (October 2009). "Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP". Neurology. 73 (17): 1348–1352. doi:10.1212/WNL.0b013e3181bd1139. PMID 19776380. S2CID 207116106.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.