Receptor cluster formation during activation by bacterial products.
The recognition of bacterial products, such as lipopolysaccharide (LPS) by the innate immune system lead to a strong pro-inflammatory response that can eventually lead to fatal sepsis syndrome in humans. Although CD14 and TLR4 have been identified as the key molecules involved in LPS-induced signal transduction, accumulating evidence indicates that multiple receptors are also involved. Our group has recently identified a cluster of receptors, involving heat-shock proteins 70 and 90, chemokine receptor 4 as well as growth differentiation factor 5, that are formed following LPS stimulation. In addition, we present data demonstrating that these molecules associate with TLR4 and accumulate in membrane microdomains following LPS ligation. Our results suggest that the entire bacterial recognition is based around the recruitment of multiple signalling molecules, in addition to CD14 and TLRs, within the lipid rafts. We propose that different combinational associations of receptors within activation clusters determine the different responses to a variety of bacterial stimuli.
Institute of Biomedical and Biomolecular Sciences, School of Biological Sciences, University of Portsmouth, Portsmouth, UK. kathy.triantafilou@port.ac.uk
Martha
M
Triantafilou
Kathy
K
Triantafilou
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016466:CHO Cells; D002846:Chromatography, Affinity; D006224:Cricetinae; D003412:Cricetulus; D031541:Fluorescence Resonance Energy Transfer; D055428:Growth Differentiation Factor 5; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D012475:Salmonella / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C085483:Re lipopolysaccharide; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors