Editors' ChoiceReceptor biology

Pre-paired Receptors

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Science's STKE  04 Jul 2000:
Vol. 2000, Issue 39, pp. tw2
DOI: 10.1126/stke.2000.39.tw2

A fundamental biological question that remains largely unresolved concerns the mechanism by which binding of ligands to receptors on the cell surface causes transmission of a signal through the plasma membrane. One appealing explanation has been that ligand binding brings receptors together into multimeric complexes. Three reports describe cases in which the opposite approach is taken, and the receptors are bound and lie in wait for the ligand. Siegel et al. and Chan et al. have examined how the Fas and tumor necrosis factor (TNF) receptors signal. They define a protein interaction domain in these receptors that mediates assembly of the receptors into complexes in the absence of ligand. Such association is shown to be necessary for ligand binding and subsequent signaling. The results also explain how abnormal forms of Fas can dominantly prevent Fas-induced signaling in the human disease known as autoimmune lymphoproliferative syndrome. When bound to their cognate receptors, interferons (IFNs) induce cellular resistance to viral infection. Takaoka et al. show that certain cells, if they are to maximize this response when exposed to the cytokine IFN-γ, must express not only a functional IFN-γ receptor but a functional IFN-α/β receptor as well. Before these cells are even stimulated with IFN-γ, the IFN-γ receptor is preassociated with the IFN-α/β receptor. The IFN-α/β receptor brings a transcription activator to the complex that is poised to become activated upon stimulation with IFN-γ. Cross talk between two IFN receptor subtypes appears to increase the efficiency and strength of a cell's antiviral response to IFN-γ. A Perspective by Golstein discusses pre-clustering of receptors before activation.

Siegel, R.M., Frederiksen, J.K., Zacharias, D.A.,Chan, F.K.-M., Johnson, M., Lynch, D., Tsien, R.Y., and Lenardo, M.J. (2000) Fas preassociation required for apoptosis signaling and dominant inhibition by pathogenic mutations. Science 288: 2354-2357. [Abstract] [Full Text]

Chan, F.K.-M., Chun, H.J., Zheng, L., Siegel, R.M., Bui, K.L., and Lenardo, M.J. (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288: 2351-2354. [Abstract] [Full Text]

Takaoka, A., Mitani, Y., Suemori, H., Sato, M., Yokochi, T., Noguchi, S., Tanaka, N., and Taniguchi, T. (2000) Cross talk between interferon-γ and -α/β signaling components in caveolar membrane domains. Science 288: 2357-2360. [Abstract] [Full Text]

Golstein, P. (2000) Signal Transduction: FasL binds preassembled Fas. Science 288: 2328-2329. [Full Text]