Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How cells degrade aberrant membrane proteins

13.07.2012
Heidelberg researchers unravel new degradation route

Researchers from Heidelberg University’s Center for Molecular Biology (ZMBH) have achieved unexpected insights into the process of how damaged proteins are degraded within cells. Their work focused on the function of a special protease.


In eukaryotic cells, misfolded membrane proteins are retained in the Endoplasmic Reticulum (ER) as assessed by immunofluorescence microscopy. The micrograph shows a damaged membrane protein in green and an ER-resident protein in red leading to various overlaps in yellow.
Image: ZMBH


The ER-resident rhomboid protease (blue) breaks up misfolded membrane proteins (green) within the membrane thereby initiating their transport to the cytosol and further degradation by the ubiquitin-proteasome system.
Image: ZMBH

This enzyme can hydrolyse peptide bonds in the plane of cellular membranes, a site where such water-requiring reactions commonly do not occur. The scientists working with Dr. Marius Lemberg could now show that this unusual protease recognises and degrades aberrant proteins directly in the membrane. The findings were published online in “Molecular Cell”.

When the research team around Dr. Lemberg started its work on a member of these special proteases they predicted by computational approaches that this enzyme would be active. However, they still faced the challenge to experimentally determine the physiological substrates. “The existing knowledge about relatives from the so-called rhomboid protease family did not help us in our quest for the molecules processed by the enzyme we discovered”, says Dr. Lemberg. Unlike all rhomboid proteases that had been studied so far, the new rhomboid localises to the Endoplasmic Reticulum (ER), the site in the cell where new membrane proteins are produced.

The breakthrough came after the researchers observed that the ER rhomboid protease is increasingly needed during protein folding stress. Proteins are produced as long chains of amino acids that have to correctly fold into a three-dimensional structure to fulfil their function. Especially when accumulating, misfolded proteins can severely damage cells and are known to cause impairments such as Alzheimer's and Parkinson's disease.

“We now have revealed that the ER rhomboid protease cleaves aberrant membrane proteins within their membrane anchor”, says Dr. Lemberg. Furthermore, the scientists demonstrated that this protease cooperates directly with components of the so-called ER-associated degradation (ERAD) pathway to dispose of the faulty protein. According to Dr. Lemberg, these new insights now provide the basis for a molecular understanding of how membrane proteins that make up a large fraction of cellular proteins are extracted from these membranes for degradation without getting into each other’s way.

The junior research group of Dr. Lemberg is part of the DKFZ-ZMBH Alliance – the strategic cooperation between the German Cancer Research Center (DKFZ) and the Heidelberg University's Center for Molecular Biology (ZMBH) – as well as of the interdisciplinary Network Aging Research (NAR) at Ruperto Carola. The group receives funding from the Baden-Württemberg Foundation.

For further information, go to: http://www.zmbh.uni-heidelberg.de/lemberg/default.shtml.

Original publication:
Lina Fleig, Nina Bergbold, Priyanka Sahasrabudhe, Beate Geiger, Lejla Kaltak, Marius K. Lemberg: Ubiquitin-Dependent Intramembrane Rhomboid Protease Promotes ERAD of Membrane Proteins. Mol. Cell (July 12, 2012), doi: 10.1016/j.molcel.2012.06.008.

Contact:
Dr. Marius Lemberg
Center for Molecular Biology of Heidelberg University (ZMBH)
DKFZ-ZMBH Alliance
Phone: +49 6221 54-5889 

m.lemberg@zmbh-heidelberg.de

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

Marietta Fuhrmann-Koch | idw
Further information:
http://www.zmbh.uni-heidelberg.de/lemberg/default.shtml
http://www.uni-heidelberg.de

More articles from Life Sciences:

nachricht Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel

nachricht Smelling the forest – not the trees
12.12.2018 | Universität 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: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

New discoveries predict ability to forecast dementia from single molecule

12.12.2018 | Health and Medicine

CCNY-Yale researchers make shape shifting cell breakthrough

12.12.2018 | Physics and Astronomy

Pain: Perception and motor impulses arise in the brain independently of one another

12.12.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>