Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Visualising Molecular Patterns of Membrane TNF Receptors

16.01.2020

Single-molecule microscopy visualises the dance of receptors

Whether a sick cell dies, divides, or travels through the body is regulated by a sophisticated interplay of signal molecules and receptors on the cell membrane. One of the most important molecular cues in the immune system is Tumour Necrosis Factor α (TNFα).


Now, for the first time, researchers from Goethe University have visualised the molecular organisation of individual TNFα receptor molecules and the binding of TNFα to the cell membrane in cells using optical microscopy.

Before TNFα can bind to a membrane receptor, the TNFR receptor must first be activated. By doing so, the key will only fit the lock under certain circumstances and prevents, among other things, that a healthy cell dies from programmed cell death.

“For TNFR1 in the membrane, the binding of TNFα is mediated through several cysteine-rich domains, or CRDs,” explains Sjoerd van Wijk form the Institute for Experimental Cancer Research in Paediatrics and the Frankfurt Stiftung für Krebskranke Kinder at Goethe University.

In particular, CRD1 of the TNFR1 makes it possible for TNFα to “attach”. Researchers already knew that TNFR1 molecules cluster in a fashion similar to a dance, in which two, three or more partners grasp hands – with the dimers, trimers or oligomers consisting of single TNFR1 mole-cules – in the case of TNFR1. This kind of “structural reorganization” also takes place when there is no TNFα present.

“Despite the significance of TNFα for many diseases, including in-flammation and cancer, the physiology and patterns of TNFR1 in the cell membrane still remain largely unknown up to now,” says Sjoerd Van Wijk, explaining the starting point for his research.

In order to understand the processes in the cell membrane in detail, van Wijk approached Mike Heilemann from the Institute for Physical and Theoretical Chemistry at Goethe University. Using a combination of quantitative microscopy and single-molecule super-resolution microscopy that he developed, Heilemann can visualise individual protein complexes as well as their molecular organisation in cells.

Together with Ivan Dikic (Institute for Biochemistry II) and Simone Fulda (Institute for Experimental Cancer Research in Paediatrics) from Goethe University, Harald Wa-jant from the University Hospital Würzburg and Darius Widera from University Reading/UK, they were able to observe the dance of the TNFα receptors.

Financial support was provided by the Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research Centre 807 “Transport and Communication across Biological Membranes”.
As the researchers report in the current issue of “Science Signalling”, membrane TNFR1 recep-tors exist as monomers and dimers in the absence of TNFα.

However, as soon as TNFα binds TNFR1, receptor trimers and oligomers are formed in the membrane. The researchers also found indications for mechanisms that determine cell fate independently of TNFα. These findings could be relevant for cancer or and inflammatory diseases such as rheumatoid arthritis. “It clear-ly opens new paths for developing novel therapeutic approaches,” states van Wijk.

Publication:C. Karathanasis, J. Medler, F. Fricke, S. Smith, S. Malkusch, D. Widera, S. Fulda, H. Wajant, S. J. L. van Wijk, I. Dikic, M. Heilemann, Single-molecule imaging reveals the oligomeric state of functional TNF-induced plasma membrane TNFR1 clusters in cells. Sci. Signal. 13, eaax5647 (2020).DOI: 10.1126/scisignal.aax5647

Wissenschaftliche Ansprechpartner:

Dr Sjoerd van Wijk, Institute for Experimental Cancer Research in Paediatrics, Niederrad Campus, Tel.: +49 69 67866574, Email: s.wijk@kinderkrebsstiftung-frankfurt.de; Prof Mike Heilemann, Institute for Physical and Theoretical Chemistry, Riedberg Campus, Tel.: +49 69 798 29424, Email: heileman@chemie.uni-frankfurt.de

Originalpublikation:

C. Karathanasis, J. Medler, F. Fricke, S. Smith, S. Malkusch, D. Widera, S. Fulda, H. Wajant, S. J. L. van Wijk, I. Dikic, M. Heilemann, Single-molecule imaging reveals the oligomeric state of func-tional TNF-induced plasma membrane TNFR1 clusters in cells. Sci. Signal. 13, eaax5647 (2020).DOI: 10.1126/scisignal.aax5647

Dr. Anke Sauter | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-frankfurt.de

More articles from Life Sciences:

nachricht Study reveals how bacteria build essential carbon-fixing machinery
09.07.2020 | University of Liverpool

nachricht Stress testing 'coral in a box'
09.07.2020 | University of Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The spin state story: Observation of the quantum spin liquid state in novel material

New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices

Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

 
Latest News

Porous graphene ribbons doped with nitrogen for electronics and quantum computing

09.07.2020 | Physics and Astronomy

Record efficiency for printed solar cells

09.07.2020 | Power and Electrical Engineering

Rock 'n' control

09.07.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>