HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 22, 15450-15456, June 2, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/22/15450    most recent M511502200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ward, E. M. Articles by Taylor, M. E. Search for Related Content PubMed PubMed Citation Articles by Ward, E. M. Articles by Taylor, M. E. Social Bookmarking                      What's this?

Polymorphisms in Human Langerin Affect Stability and Sugar Binding Activity^*

From the Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU and Division of Molecular Biosciences, Imperial College, London SW7 2AZ, United Kingdom

Langerhans cells are specialized skin dendritic cells that take up and degrade antigens for presentation to the immune system. Langerin, a cell surface C-type lectin of Langerhans cells, can be internalized and accumulates in Birbeck granules, subdomains of the endosomal recycling compartment that are specific to Langerhans cells. Langerin binds and mediates uptake and degradation of glycoconjugates containing mannose and related sugars. Analysis of the human genome has identified three single nucleotide polymorphisms that result in amino acid changes in the carbohydrate-recognition domain of langerin. The effects of the amino acid changes on the activity of langerin were examined by expressing each of the polymorphic forms. Expression of full-length versions of the four common langerin haplotypes in fibroblasts revealed that all of these forms can mediate endocytosis of neoglycoprotein ligands. However, sugar binding assays and differential scanning calorimetry performed on fragments from the extracellular domain showed that two of the amino acid changes reduce the affinity of the carbohydrate-recognition domain for mannose and decrease the stability of the extracellular domain. In addition, analysis of sugar binding by langerin containing the rare W264R mutation, previously identified in an individual lacking Birbeck granules, shows that this mutation abolishes sugar binding activity. These findings suggest that certain langerin haplotypes may differ in their binding to pathogens and thus might be associated with susceptibility to infection.

Received for publication, October 24, 2005 , and in revised form, March 6, 2006.

^* This work was supported by Wellcome Trust Grants 041845, 064235, and 075565. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Division of Molecular Biosciences, Biochemistry Bldg., Imperial College, London SW7 2AZ, UK. Tel.: 44-20-7594-5281; Fax: 44-20-7594-5207; E-mail: maureen.taylor{at}imperial.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. S. Powlesland, T. Fisch, M. E. Taylor, D. F. Smith, B. Tissot, A. Dell, S. Pohlmann, and K. Drickamer A Novel Mechanism for LSECtin Binding to Ebola Virus Surface Glycoprotein through Truncated Glycans J. Biol. Chem., January 4, 2008; 283(1): 593 - 602. [Abstract] [Full Text] [PDF]