Research ArticleCell Biology

Single-molecule imaging reveals the oligomeric state of functional TNFα-induced plasma membrane TNFR1 clusters in cells

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Science Signaling  14 Jan 2020:
Vol. 13, Issue 614, eaax5647
DOI: 10.1126/scisignal.aax5647

Oligomerizing for optimal activity

Drugs that prevent the activation of the TNFα receptor TNFR1 are of great interest because of the many roles of this ligand/receptor pair in pathophysiological processes such as inflammation. Karathanasis et al. determined the oligomerization state of TNFR1 by quantitatively analyzing single-molecule superresolution microscopy data. TNFα stimulation triggered the clustering of TNFR1 monomers and dimers into trimers and nonamers. Forms of TNFR1 with mutations that impaired basal dimerization or that abolished ligand binding did not assemble into higher-order oligomers upon TNFα stimulation. These results provide insight into the oligomerization states of TNFR1 that must be targeted before and after TNFα stimulation.

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