Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction
Fitzgerald, Katherine A.
Monks, Brian G.
Kurt-Jones, Evelyn A.
Golenbock, Douglas T.
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
KeywordsAdaptor Proteins, Signal Transducing
Dose-Response Relationship, Drug
Green Fluorescent Proteins
Lymphocyte Antigen 96
Myeloid Differentiation Factor 88
Protein Structure, Tertiary
Receptors, Cell Surface
Recombinant Fusion Proteins
Toll-Like Receptor 4
Immunology and Infectious Disease
Medicine and Health Sciences
MetadataShow full item record
AbstractMammalian responses to LPS require the expression of Toll-like receptor 4 (TLR4), CD14, and MD-2. We expressed fluorescent TLR4 in cell lines and found that TLR4 densely localized to the surface and the Golgi. Similar distributions were observed in human monocytes. Confocal imaging revealed rapid recycling of TLR4-CD14-MD-2 complexes between the Golgi and the plasma membrane. Fluorescent LPS followed these trafficking pathways in CD14-positive cells. The TLR4- adapter protein, MyD88, translocated to the cell surface upon LPS exposure, and cross-linking of surface TLR4 with antibody induced signaling. Golgi-associated TLR4 expression was disrupted by brefeldin A, yet LPS signaling was preserved. We conclude that LPS signaling may be initiated by surface aggregation of TLR4 and is not dependent upon LPS trafficking to the Golgi.
SourceJ Biol Chem. 2002 Dec 6;277(49):47834-43. Epub 2002 Sep 24. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42372
Related ResourcesLink to Article in PubMed
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