Heidelberg researchers study process of marking and cellular waste disposal
In their research on protein quality control, Heidelberg scientists gained new insights into how the cell keeps proteins misdirected into the cell nucleus from causing damage. Their investigations focussed on a complex apparatus on the inner nuclear membrane that detects and marks the misdelivered proteins.
In an international cooperation with researchers from France, Sweden and Canada, the team under the direction of Prof. Dr. Michael Knop at the Center for Molecular Biology of Heidelberg University (ZMBH) demonstrated how the cellular “waste disposal service” is triggered in this process. The results of their research were published in “Nature”.
Cells are quite small, but nevertheless very precisely organised in terms of structure – everything has its place. To find their proper place, proteins bear a type of signal built into their structure. These signals function like addresses, and the intracellular “postal service” delivers them to the correct destination. One of these destinations is the cell nucleus. It contains genomic information – the cell DNA.
The DNA has to be read and decoded into new proteins in order for the cell to divide and respond to its environment. The nuclear proteins ensure this process runs correctly. But what happens when proteins accidently find their way into the cell nucleus even though they do not belong there? “This endangers the reading of the genomic information and under certain conditions threatens the existence of the entire cell,” explains Prof. Knop, who heads the yeast cell and systems biology research group at the ZMBH.
During the course of their investigations, Prof. Knop’s research group developed a new method of detecting the misguided proteins and studying how the cell handles them. In collaboration with two research labs, from Rennes and Stockholm, the Heidelberg team at the ZMBH found that the cell contains a complex apparatus on the inner nuclear membrane, a ubiquitin ligase that participates in protein quality control. The ligase can detect and mark the incorrect proteins. Based on this so-called polyubiquitination, the cell “knows” that this particular protein does not belong in the nucleus and activates cellular waste disposal. A proteasome almost literally swallows and “digests” the marked proteins.
“Until now we assumed that the ubiquitin ligase we studied was linked to a special signal transmission process involved in supplying the cell with amino acids,” says Prof. Knop. “We were all the more surprised when our research showed that they actually do not directly perform this function.” Instead, the ligase triggers the removal of a protein that would disrupt the amino acid supply should it arrive in the nucleus at the wrong time.
The Heidelberg scientist further explains that this “sophisticated control mechanism” also works with various other proteins. If they are not delivered correctly, the ubiquitin ligase sets off the process of removing the misdirected proteins from the cell nucleus and the nuclear membrane. Prof. Knop: “But this question still remains: How can this ubiquitin ligase tell whether the proteins have landed in the right or the wrong place?”
Michael Knop also heads the cell morphogenesis and signal transduction working group at the German Cancer Research Center (DKFZ). The researchers from Heidelberg University and the DKFZ collaborated in this study with scientists from the National Centre for Scientific Research in Rennes and the University of Rennes, the Stockholm University, the European Molecular Biology Laboratory (EMBL) in Heidelberg and the University of Toronto.
A. Khmelinskii, E. Blaszczak, M. Pantazopoulou, B. Fischer, D.J. Omnus, G. Le Dez, A. Brossard, A. Gunnarsson, J.D. Barry, M. Meurer, D. Kirrmaier, C. Boone, W. Huber, G. Rabut, P.O. Ljungdahl, M. Knop: Protein quality control at the inner nuclear membrane, Nature 516, 410-413 (18 December 2014), doi: 10.1038/nature14096
Prof. Dr. Michael Knop
Center for Molecular Biology of Heidelberg University
Phone: +49 6221 54-4213
Communications and Marketing
Press Office, phone: +49 6221 54-2311
Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Materials Sciences
19.07.2018 | Earth Sciences
19.07.2018 | Life Sciences