Visualizing Molecular Patterns of Membrane TNF Receptors using single-molecule microscopy

The question of whether a sick cell dies, divides, or travels through the body is regulated by signal molecules that bind and activate receptors on the cell membrane. Among the most important molecular cues in the immune system is Tumor Necrosis Factor α (TNFα) that binds to TNFα receptor 1 (TNFR1). Now, Dr. Sjoerd van Wijk from the Institute for Experimental Cancer Research in Pediatrics/Frankfurt Stiftung für krebskranke Kinder, together with Mike Heilemann (Institute for Physical and Theoretical Chemistry, Goethe University), Ivan Dikic (Institute for Biochemistry II, Goethe University), Simone Fulda (Institute for Experimental Cancer Research in Pediatrics, Goethe University), Harald Wajant (University Hospital Würzburg) and Darius Widera (University Reading/UK), visualized for the first time the molecular organization of individual TNFR1 molecules using quantitative single-molecule super-resolution microscopy. As reported by the researchers in the current issue of the internationally renowned peer-reviewed journal “Science Signaling”, membrane TNFR1 exist as monomers and dimers in the absence of TNFα, however, TNFα binding creates TNFR1 trimers and oligomers. These findings provide novel insights in intrinsic TNFR1 clustering in the absence of TNFα, highlighting the relevance of coordinated TNFR1 clustering for cancer development and chronic inflammatory diseases, such as rheumatoid arthritis. “It clearly opens new avenues for developing novel therapeutic approaches,” states van Wijk.

Link to article:

https://stke.sciencemag.org/content/13/614/eaax5647?utm_campaign=toc_signaling_2020-01-14&et_rid=17777426&et_cid=3163658

Further information: Dr Sjoerd van Wijk, Institute for Experimental Cancer Research in Pediatrics, Tel.: +49 69 67866574, Email: s.wijk@kinderkrebsstiftung-frankfurt.de

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