Difference between revisions of "LSECtin"
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=== Glycogene microarray === | === Glycogene microarray === | ||
| + | Probes for LSECtin have been included in version 4 of the CFG glycogene chip [human probeset NM_198492/mouse probeset NM_029465]. | ||
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=== Knockout mouse lines === | === Knockout mouse lines === | ||
LSECtin knockout mice were created by the CFG ([https://www.functionalglycomics.org/static/consortium/resources/DataCoreFCG.shtml LSECtin-total knockout] and [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFCG.shtml LSECtin-conditional knockout]) and are in the queue for [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotype] analysis in 2010/11. | LSECtin knockout mice were created by the CFG ([https://www.functionalglycomics.org/static/consortium/resources/DataCoreFCG.shtml LSECtin-total knockout] and [https://www.functionalglycomics.org/static/consortium/resources/DataCoreFCG.shtml LSECtin-conditional knockout]) and are in the queue for [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotype] analysis in 2010/11. | ||
Revision as of 10:05, 6 June 2010
LSECtin serves a model for other members of the C-type lectin family that are expressed on sinusoidal endothelial cells and facilitate viral infection, but lack endocytic function. The other main example of a protein with these characteristics is DC-SIGNR or L-SIGN, which is expressed in similar places and is also a target for various viruses, but has a different organization and ligand-binding characteristics.
CFG Participating Investigators contributing to the understanding of this paradigm
Several PIs are working on ligand-binding specificity of LSECtin and interaction of this C-type lectin with viral pathogens.
- PIs working on LSECtin include: Angel Corbi, Kurt Drickamer, Maureen Taylor
- PIs working on L-SIGN/DC-SIGNR include: Ben Appelmelk, Angel Corbi, Kurt Drickamer, Benhur Lee, Maureen Taylor, Yvette van Kooyk, Bill Weis
Progress toward understanding this GBP paradigm
Carbohydrate ligands
A major contribution from the CFG has been identification of the motif GlcNAcβ1-2Man as a common motif in all of the high affinity ligands. Competition studies have revealed that the affinity for this disaccharide is approximately 2 μM, making it one of the most specific and high affinity interactions known for any C-type lectin[1]. The glycoprotein CD44 on T cells has been identified as a potential glycoprotein ligand[2]
Cellular expression
Expression of LSECtin was originally described in sinusoidal endothelial cells of liver, lymph node and bone[3]. Subsequence studies have revealed expression in Kupffer cells in the liver as well[4]. Expression can also be induced in dendritic cell and macrophages under some conditions in vitro[5].
Structure
LSECtin is a type II transmembrane protein, with a C-terminal C-type carbohydrate-recognition domain (CRD) projected from the membrane surface by an intermediate neck domain. The short C-terminal domain is devoid of obvious signaling or internalization motifs. The receptor appears to be a disulfide-linked dimer[1].
Biological roles of GBP-ligand interaction
The natural role of LSECtin is poorly understood. The receptor does not undergo constitutive recycling endocytosis, but binding of antibodies or ligands may lead to triggered internalization[1][3]. It has been suggested that in the liver LSECtin is an adhesion receptor that binds to CD44 on T cells and suppresses activation of T cells, thus contributing to general immune tolerance in the liver[6].
CFG resources used in investigations
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for LSECtin.
Glycan profiling
Glycan profiling of mouse EL4 T lymphocytes shows that several of the most abundant glycans present bear terminal GlcNAcβ1-2Man structures which would be potential ligands for LSECtin.
Glycogene microarray
Probes for LSECtin have been included in version 4 of the CFG glycogene chip [human probeset NM_198492/mouse probeset NM_029465].
Knockout mouse lines
LSECtin knockout mice were created by the CFG (LSECtin-total knockout and LSECtin-conditional knockout) and are in the queue for phenotype analysis in 2010/11.
Glycan array
Glycan array analysis of LSECtin has revealed unusually high selectivity for specific ligands.
Related GBPs
L-SIGN / DC-SIGNR
References
- ↑ 1.0 1.1 1.2 Powlesland AS, Fisch T, Taylor ME, Smith DF, Tissot B, Dell A, Pöhlmann S, Drickamer K. (2008) A novel mechanism for LSECtin binding to Ebola virus surface glycoprotein through truncated glycans. J Biol Chem 283, 593-602
- ↑ Tang L, Yang J, Tang X, Ying W, Qian X, He F (2010) The DC-SIGN family member LSECtin is a novel ligand of CD44 on activated T cells. Eur J Immunol 40, 1185-1191
- ↑ 3.0 3.1 Liu W, Tang L, Zhang G, Wei H, Cui Y, Guo L, Gou Z, Chen X, Jiang D, Zhu Y, Kang G, He F. (2004) Characterization of a novel C-type lectin-like gene, LSECtin: demonstration of carbohydrate binding and expression in sinusoidal endothelial cells of liver and lymph node. J Biol Chem 279, 18748-18758
- ↑ Dominguez-Soto A, Aragoneses-Fenoll L, Martin-Gayo E, Martinez-Prats L, Colmenares M, Naranjo-Gomez M, Borras FE, Munoz P, Zubiaur M, Toribio ML, Delgado R, Corbi AL (2007) The DC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells. Blood 109, 5337-5345
- ↑ Domínguez-Soto A, Aragoneses-Fenoll L, Gómez-Aguado F, Corcuera MT, Clária J, García-Monzón C, Bustos M, Corbí AL (2009) The pathogen receptor liver and lymph node sinusoidal endothelial cell C-type lectin is expressed in human Kupffer cells and regulated by PU.1. Hepatology 49, 287-296
- ↑ Tang L, Yang J, Liu W, Tang X, Chen J, Zhao D, Wang M, Xu F, Lu Y, Liu B, Sun Q, Zhang L, He F (2009) Liver sinusoidal endothelial cell lectin, LSECtin, negatively regulates hepatic T-cell immune response. Gastroenterology 137, 1498-1508
Powlesland AS, Fisch T, Taylor ME, Smith DF, Tissot B, Dell A, Phölmann S, Drickamer K (2008) A novel mechanism for LSECtin binding to Ebola virus surface glycoprotein through truncated glycans. J Biol Chem 283, 593-602.
Acknowledgements
The CFG is grateful to the following PIs for their contributions to this wiki page: Kurt Drickamer, Yvette van Kooyk
