Historical Background
CLEC5A is a type 2 transmembrane receptor originally identified by its ability to stabilize DAP (DNAX associating protein)-12 at the cell surface in myeloid cells (Bakker et al. 1999). It is emerging as a key component of the innate immune system; it activates macrophages, regulates osteoclastogenesis, and plays a role in inflammatory diseases including dengue virus-induced lethality, Japanese encephalitis-associated neuro-inflammation, and autoimmune arthritis (Bakker et al. 1999; Chen et al. 2008; Aoki et al. 2009; Joyce-Shaikh et al. 2010; Chen et al. 2012).
Structure
The predicted 161 amino acid extracellular sequence of CLEC5A contains a C-type lectin-like domain in the carboxy-terminal region (UniProt 2015). The N-terminal cytoplasmic tail is predicted to...
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Aoki N, Kimura S, Xing Z. Role of DAP12 in innate and adaptive immune responses. Curr Pharm Des. 2003;9:7–10.
Aoki N, Kimura Y, Kimura S, Nagato T, Azumi M, Kobayashi H, et al. Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage cells. J Leukoc Biol. 2009;85:508–17. https://doi.org/10.1189/jlb.0508329.
Aoki N, Zganiacz A, Margetts P, Xing Z. Differential regulation of DAP12 and molecules associated with DAP12 during host responses to mycobacterial infection. Infect Immun. 2004;72:2477–83.
Bakker AB, Baker E, Sutherland GR, Phillips JH, Lanier LL. Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc Natl Acad Sci USA. 1999;96:9792–6.
Bakker AB, Hoek RM, Cerwenka A, Blom B, Lucian L, McNeil T, et al. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity. 2000;13:345–53. https://doi.org/10.1016/S1074-7613(00)00034-0.
Batliner J, Mancarelli MM, Jenal M, Reddy VA, Fey MF, Torbett BE, et al. CLEC5A (MDL-1) is a novel PU.1 transcriptional target during myeloid differentiation. Mol Immunol. 2011;48:714–9. https://doi.org/10.1016/j.molimm.2010.10.016.
Chen DY, Yao L, Chen YM, Lin CC, Huang KC, Chen ST, et al. A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients. PLoS One. 2014;9:e86105. https://doi.org/10.1371/journal.pone.0086105.
Chen ST, Lin YL, Huang MT, Wu MF, Cheng SC, Lei HY, et al. CLEC5A is critical for dengue-virus-induced lethal disease. Nature. 2008;453:672–6. https://doi.org/10.1038/nature07013.
Chen ST, Liu RS, Wu MF, Lin YL, Chen SY, Tan DT, et al. CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality. PLoS Pathog. 2012;8:e1002655. https://doi.org/10.1371/journal.ppat.1002655.
Cheung R, Shen F, Phillips JH, McGeachy MJ, Cua DJ, Heyworth PG, et al. Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice. J Clin Invest. 2011;121:4446–61. https://doi.org/10.1172/JCI57682.
Consortium CAD, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013;45:25–33. https://doi.org/10.1038/ng.2480.
Genomes Project C, Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491:56–65. https://doi.org/10.1038/nature11632.
Gingras MC, Lapillonne H, Margolin JF. TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development. Mol Immunol. 2002;38:817–24. doi:10.1016/S0161589002000044 [pii].
Gonzalez-Dominguez E, Samaniego R, Flores-Sevilla JL, Campos-Campos SF, Gomez-Campos G, Salas A, et al. CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo. J Leukoc Biol. 2015;98:453–66. https://doi.org/10.1189/jlb.3HI1114-531R.
Gupta N, Lomash V, Rao PV. Expression profile of Japanese encephalitis virus induced neuroinflammation and its implication in disease severity. J Clin Virol. 2010;49:4–10. https://doi.org/10.1016/j.jcv.2010.06.009.
Hruba P, Brabcova I, Gueler F, Krejcik Z, Stranecky V, Svobodova E, et al. Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes. Kidney Int. 2015;88:785–95. https://doi.org/10.1038/ki.2015.211.
Huang YL, Chen ST, Liu RS, Chen YH, Lin CY, Huang CH, et al. CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis. J Mol Med (Berl). 2016; https://doi.org/10.1007/s00109-016-1409-0.
Inui M, Kikuchi Y, Aoki N, Endo S, Maeda T, Sugahara-Tobinai A, et al. Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proc Natl Acad Sci U S A. 2009;106:4816–21. https://doi.org/10.1073/pnas.0900463106.
Joyce-Shaikh B, Bigler ME, Chao CC, Murphy EE, Blumenschein WM, Adamopoulos IE, et al. Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis. J Exp Med. 2010;207:579–89. https://doi.org/10.1084/jem.20090516.
Lanier LL. DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev. 2009;227:150–60. https://doi.org/10.1111/j.1600-065X.2008.00720.x.
Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008;9:495–502. https://doi.org/10.1038/ni1581.
Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 1998;391:703–7. https://doi.org/10.1038/35642.
Maglott D, Ostell J, Pruitt KD, Tatusova T. Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res. 2007;35:D26–31. https://doi.org/10.1093/nar/gkl993.
Shin HS, Sarin R, Dixit N, Wu J, Gershwin E, Bowman EP, et al. Crosstalk among IL-23 and DNAX activating protein of 12 kDa-dependent pathways promotes osteoclastogenesis. J Immunol. 2015;194:316–24. https://doi.org/10.4049/jimmunol.1401013.
Tybulewicz VL. Vav-family proteins in T-cell signalling. Curr Opin Immunol. 2005;17:267–74. https://doi.org/10.1016/j.coi.2005.04.003.
UniProt C. UniProt: a hub for protein information. Nucleic Acids Res. 2015;43:D204–12. https://doi.org/10.1093/nar/gku989.
Upshaw JL, Arneson LN, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ. NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nat Immunol. 2006;7:524–32. https://doi.org/10.1038/ni1325.
Watson AA, Lebedev AA, Hall BA, Fenton-May AE, Vagin AA, Dejnirattisai W, et al. Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling. J Biol Chem. 2011;286:24208–18. https://doi.org/10.1074/jbc.M111.226142.
Watson AA, O’Callaghan CA. Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue virus receptor. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010;66:29–31. https://doi.org/10.1107/S1744309109047915.
Wortham BW, Eppert BL, Flury JL, Garcia SM, Donica WR, Osterburg A, et al. Cutting Edge: CLEC5A Mediates Macrophage Function and Chronic Obstructive Pulmonary Disease Pathologies. J Immunol. 2016;196:3227–31. https://doi.org/10.4049/jimmunol.1500978.
Wu MF, Chen ST, Yang AH, Lin WW, Lin YL, Chen NJ, et al. CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages. Blood. 2013;121:95–106. https://doi.org/10.1182/blood-2012-05-430090.
Xavier-Carvalho C, Gibson G, Brasil P, Ferreira RX, de Souza SR, Goncalves Cruz O, et al. Single nucleotide polymorphisms in candidate genes and dengue severity in children: a case-control, functional and meta-analysis study. Infect Genet Evol. 2013;20:197–205. https://doi.org/10.1016/j.meegid.2013.08.017.
Yang YL, Chang WP, Hsu YW, Chen WC, Yu HR, Liang CD, et al. Lack of association between CLEC5A gene single-nucleotide polymorphisms and Kawasaki disease in Taiwanese children. J Biomed Biotechnol. 2012;2012:398628. https://doi.org/10.1155/2012/398628.
Yim D, Jie HB, Sotiriadis J, Kim YS, Kim YB. Molecular cloning and expression pattern of porcine myeloid DAP12-associating lectin-1. Cell Immunol. 2001;209:42–8. https://doi.org/10.1006/cimm.2001.1782.
Zeller T, Wild P, Szymczak S, Rotival M, Schillert A, Castagne R, et al. Genetics and beyond--the transcriptome of human monocytes and disease susceptibility. PLoS One. 2010;5:e10693. https://doi.org/10.1371/journal.pone.0010693.
Zollbrecht C, Grassl M, Fenk S, Hocherl R, Hubauer U, Reinhard W, et al. Expression pattern in human macrophages dependent on 9p21.3 coronary artery disease risk locus. Atherosclerosis. 2013;227:244–9. https://doi.org/10.1016/j.atherosclerosis.2012.12.030.
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Reschen, M.E., O’Callaghan, C.A. (2018). CLEC5A. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_572
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DOI: https://doi.org/10.1007/978-3-319-67199-4_572
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