Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting

Martha Triantafilou, Frederick G J Gamper, Rowenna M. Haston, Marios Angelos Mouratis, Siegfried Morath, Thomas Hartung, Kathy Triantafilou

Research output: Contribution to journalArticle

Abstract

Toll-like receptors (TLRs) are receptors of the innate immune system responsible for recognizing pathogen-associated molecular patterns. TLR2 seems to be the most promiscuous TLR receptor able to recognize the most diverse set of pathogen-associated patterns. Its promiscuity has been attributed to its unique ability to heterodimerize with TLRs 1 and 6 and, most recently, to its association with CD36 in response to diacylated lipoproteins. Thus, it seems that TLR2 forms receptor clusters in response to different microbial ligands. In this study we investigated TLR2 cell surface heterotypic interactions in response to different ligands as well as internalization and intracellular trafficking. Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand. Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts. In contrast, heterotypic associations of TLR2/6 with CD36 are not preformed and are ligand-induced. All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus. This localization and targeting is ligand-specific. Activation occurs at the cell surface, and the observed trafficking is independent of signaling.

Original languageEnglish (US)
Pages (from-to)31002-31011
Number of pages10
JournalJournal of Biological Chemistry
Volume281
Issue number41
DOIs
StatePublished - Oct 13 2006
Externally publishedYes

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Toll-Like Receptor 6
Toll-Like Receptor 2
Sorting
Ligands
Membranes
Toll-Like Receptors
Toll-Like Receptor 1
Lipids
Immune system
Golgi Apparatus
Pathogens
Lipoproteins
Immune System
Chemical activation
Association reactions

ASJC Scopus subject areas

  • Biochemistry

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Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. / Triantafilou, Martha; Gamper, Frederick G J; Haston, Rowenna M.; Mouratis, Marios Angelos; Morath, Siegfried; Hartung, Thomas; Triantafilou, Kathy.

In: Journal of Biological Chemistry, Vol. 281, No. 41, 13.10.2006, p. 31002-31011.

Research output: Contribution to journalArticle

Triantafilou, Martha ; Gamper, Frederick G J ; Haston, Rowenna M. ; Mouratis, Marios Angelos ; Morath, Siegfried ; Hartung, Thomas ; Triantafilou, Kathy. / Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 41. pp. 31002-31011.
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