Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How the Cell Keeps Misdelivered Proteins From Causing Damage in the Cell Nucleus

18.12.2014

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.

Original publication:
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

Contact:
Prof. Dr. Michael Knop
Center for Molecular Biology of Heidelberg University
Phone: +49 6221 54-4213
m.knop@zmbh.uni-heidelberg.de

Communications and Marketing
Press Office, phone: +49 6221 54-2311
presse@rektorat.uni-heidelberg.de

Weitere Informationen:

http://www.zmbh.uni-heidelberg.de/knop

Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

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 fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>