LSECtin - Revision history

Carole Weaver at 21:36, 18 March 2011

2011-03-18T21:36:59Z

Kurt Drickamer at 19:57, 7 March 2011

2011-03-07T19:57:52Z

Kurt Drickamer at 19:28, 7 March 2011

2011-03-07T19:28:20Z

Kurt Drickamer at 19:19, 7 March 2011

2011-03-07T19:19:27Z

Carole Weaver: /* Cellular expression of GBP and ligands */

2010-08-31T17:14:56Z

Cellular expression of GBP and ligands

Carole Weaver: /* Progress toward understanding this GBP paradigm */

2010-08-06T16:54:20Z

Progress toward understanding this GBP paradigm

Carole Weaver: /* Glycan array */

2010-07-19T16:48:32Z

Glycan array

Carole Weaver: /* Glycan array */

2010-07-19T16:48:08Z

Glycan array

Kurt Drickamer: /* Knockout mouse lines */

2010-07-19T15:55:18Z

Knockout mouse lines

Kurt Drickamer: /* Glycan array */

2010-07-19T15:54:35Z

Glycan array

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 === Glycan array ===
-Glycan array results for human LSECtin reveal a remarkable specificity for glycans containing one or more terminal GlcNAc&beta;1-2Man sequences ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1043 example]). See all glycan array results for LSECtin [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=LSECtin&cat=coreh here].
+Glycan array results for human LSECtin reveal a remarkable specificity for glycans containing one or more terminal GlcNAc&beta;1-2Man sequences ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1043 example]). See all glycan array results for LSECtin [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=LSECtin&cat=coreh here]. See glycan array results for the related GBP DC-SIGNR [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=DC-SIGNR&cat=coreh here.]
 == Related GBPs ==

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 === Biosynthesis of ligands ===
 <br>
 === Structure ===

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 <br>
 === 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<ref name="Powlesland 2008"/><ref name="Liu 2004"/>. 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<ref name="Tang 2009">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. <i>Gastroenterology</i> <b>137</b>, 1498-1508</ref>.
+Unlike many cell surface glycan-binding receptors, LSECtin does not undergo constitutive recycling endocytosis, but binding of antibodies or ligands may lead to triggered internalization<ref name="Powlesland 2008"/><ref name="Liu 2004"/>. 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<ref name="Tang 2009">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. <i>Gastroenterology</i> <b>137</b>, 1498-1508</ref>.
 <br><br>
-LSECtin is able to bind to envelope glycoproteins of Ebola virus and SARS coronavirus, which may be important either in infection or in presentation of virus to other cells<ref name="Gramberg 2005">Gramberg T, Hofmann H, Möller P, Lalor PF, Marzi A, Geier M, Krumbiegel M, Winkler T, Kirchhoff F, Adams DH, Becker S, Münch J, Pöhlmann S. (2005) LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus. <i>Virology</i> <b>340</b>, 224-236</ref><ref name="Gramberg 2008">Gramberg T, Soilleux E, Fisch T, Lalor PF, Hofmann H, Wheeldon S, Cotterill A, Wegele A, Winkler T, Adams DH, Pöhlmann S. (2008) Interactions of LSECtin and DC-SIGN/DC-SIGNR with viral ligands: Differential pH dependence, internalization and virion binding. <i>Virology</i> <b>373</b>, 189-201</ref>.
+LSECtin is able to bind to envelope glycoproteins of Ebola virus and SARS coronavirus, which can be important either in infection or in presentation of virus to other cells<ref name="Gramberg 2005">Gramberg T, Hofmann H, Möller P, Lalor PF, Marzi A, Geier M, Krumbiegel M, Winkler T, Kirchhoff F, Adams DH, Becker S, Münch J, Pöhlmann S. (2005) LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus. <i>Virology</i> <b>340</b>, 224-236</ref><ref name="Gramberg 2008">Gramberg T, Soilleux E, Fisch T, Lalor PF, Hofmann H, Wheeldon S, Cotterill A, Wegele A, Winkler T, Adams DH, Pöhlmann S. (2008) Interactions of LSECtin and DC-SIGN/DC-SIGNR with viral ligands: Differential pH dependence, internalization and virion binding. <i>Virology</i> <b>373</b>, 189-201</ref>.
 <br>

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 <br>
 === 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<ref name="Powlesland 2008"/>.
 <br>

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 === Cellular expression of GBP and ligands ===
-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. <i>J Biol Chem</i> <b>279</b>, 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. <i>Blood</i> <b>109</b>, 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. <i>Hepatology</i> <b>49</b>, 287-296</ref>. The glycoprotein CD44, a potential ligand, is expressed by T cells<ref name="Tang 2010"/>.
+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. <i>J Biol Chem</i> <b>279</b>, 18748-18758</ref>. Subsequent 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. <i>Blood</i> <b>109</b>, 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. <i>Hepatology</i> <b>49</b>, 287-296</ref>. The glycoprotein CD44, a potential ligand, is expressed by T cells<ref name="Tang 2010"/>.
 <br>

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 == Progress toward understanding this GBP paradigm ==
+This section documents what is currently known about LSECtin, its carbohydrate ligand(s), and how they interact to mediate cell communication. Further information about LSECtin can be found in its [http://www.functionalglycomics.org/glycomics/molecule/jsp/viewGbpMolecule.jsp?gbpId=cbp_hum_Ctlect_416&sideMenu=no GBP Molecule Page] in the CFG database.
 === Carbohydrate ligands ===
 A major contribution from the CFG has been identification of the motif GlcNAc&beta;1-2Man as a common motif in all of the high affinity ligands. Competition studies have revealed that the affinity for this disaccharide is approximately 2 &mu;M, making it one of the most specific and high affinity interactions known for any C-type lectin<ref name="Powlesland 2008">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. <i>J Biol Chem</i> <b>283</b>, 593-602</ref>. The glycoprotein CD44 on T cells has been identified as a potential glycoprotein ligand<ref name="Tang 2010">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. <i>Eur J Immunol</i> <b>40</b>, 1185-1191</ref>.

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 === Glycan array ===
-Glycan array results for human LSECtin reveal a remarkable specificity for glycans containing one or more terminal GlcNAc&beta;1-2Man sequences (for example, [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1043 click here]). To see all glycan array results for LSECtin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=LSECtin&cat=coreh here].
+Glycan array results for human LSECtin reveal a remarkable specificity for glycans containing one or more terminal GlcNAc&beta;1-2Man sequences ([http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_1043 example]). To see all glycan array results for LSECtin, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=LSECtin&cat=coreh here].
 == Related GBPs ==

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 === 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.
 === Glycan array ===