Difference between revisions of "LSECtin"
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=== Cellular expression === | === Cellular expression === | ||
| + | Expression of LSECtin was originally described in sinusoidal endothelial cells of liver, lymph node and bone<ref name="Liu 2004">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. <b>J Biol Chem</b> <i>279</i>, 18748-18758</ref>. Subsequence studies have revealed expression in Kupffer cells in the liver as well<ref name="Dominguez-Soto 2007">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. <b>Blood</b> <i>109</i>, 5337-5345</ref>. Expression can also be induced in dendritic cell and macrophages under some conditions in vitro<ref name="Dominguez-Soto 2009">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. <b>Hepatology</b> <i>49</i>, 287-296</ref>. | ||
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=== Structure === | === Structure === | ||
Revision as of 10:01, 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
Biological roles of GBP-ligand interaction
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
Glycogene microarray
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
- ↑ 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
- ↑ 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
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
