Translocation of the IL-1 receptor to focal adhesions is regulated through the C-terminal end of the cytoplasmic domain.
The mechanisms of translocation of the IL-1 receptor to focal adhesions were analysed using EGFP reporter constructs and confocal microscopy. In fibronectin-attached cells, the receptor fusion protein was present in distinct punctate areas, co-localizing with the transmembrane-linkage protein vinculin. In migrating cells, the two proteins co-localized at the leading edge in ruffle-like structures. Experiments using a series of receptor mutants revealed that translocation of the IL-1 receptor to focal adhesions was dependent on motifs conserved between members of the TIR family, in the C-terminal end of the receptor. Further, an enhanced level of expression of the wild-type receptor at attachment sites was shown to correlate with an increased severity of IL-1 induced structural effects. This report demonstrates that translocation of the IL-1 receptor to focal adhesions is dependent on conserved domains in the C-terminal end of the protein, and that receptor localization at these sites is important in structural regulation of IL-1 mediated responses.
Huang
W Y
WY
Functional Genomics, Division of Molecular and Genetic Medicine, University of Sheffield, UK.
Vallés
S
S
Qwarnstrom
E E
EE
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D016296:Mutagenesis / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016596:Vinculin / Q000502:physiology
D005353:Fibronectins; D008164:Luminescent Proteins; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D016596:Vinculin; D049452:Green Fluorescent Proteins