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J. Biol. Chem., Vol. 279, Issue 39, 40882-40889, September 24, 2004
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**
From the
Infection and Immunity Group, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom, the Department of Immunology and Cell Biology, Research Center Borstel, Parkallee 22, Borstel D-23845, Germany, the ¶Department of Food Material Science, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, United Kingdom, and the ||Department of Biochemical Pharmacology, University of Konstanz, Konstanz D-78457, Germany
Lipoteichoic acid (LTA), a key cell wall component of Gram-positive bacteria, seems to function as an immune activator with characteristics very similar to lipopolysaccharide from Gram-negative bacteria. It has been shown that LTA binds CD14 and triggers activation via Toll-like receptor 2, but whether the activation occurs at the cell surface or internalization is required to trigger signaling has yet to be demonstrated. In this work we have investigated LTA binding and internalization and found that LTA and its receptor molecules accumulate in lipid rafts and are subsequently targeted rapidly to the Golgi apparatus. This internalization seems to be lipid raft-dependent because raft-disrupting drugs inhibited LTA/Toll-like receptor 2 colocalization in the Golgi. Similarly to lipopolysaccharide, LTA activation occurs at the cell surface, and the observed trafficking is independent of signaling.
Received for publication, January 15, 2004 , and in revised form, July 6, 2004.
* This work was supported by the Wellcome Trust (to K. T.) and German Research Foundation Grant He 2758/3-1 (to H. H.). 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.
** To whom correspondence should be addressed: School of Life Sciences, University of Sussex, JMS Bldg., Falmer, Brighton BN1 9QG, United Kingdom. Tel.: 44-1273-678-362 or 923; Fax: 44-1273-678-362; E-mail: K.Triantafilou{at}sussex.ac.uk.
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