Several human neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s disease but also ageing, are linked to an accumulation of abnormal and aggregated proteins in cells.
Cellular “garbage” can be removed from cells by sweeping them to a cellular recycling station known as the lysosome. Scientists at the Max Planck Institute of Biochemistry in Martinsried, Germany, now discovered a new family of helper proteins that recognize labeled cellular protein waste and guide them efficiently to the lysosome for destruction and subsequent recycling into their reusable compounds.
Proteins, the components of our body that execute, control and organize basically all functions in our cells, are made out of strings of amino acids, which – like an origami - are folded into specific and complex three-dimensional structures according to their desired functions.
However, since folding and maintaining of such structures is highly sensitive to cellular or environmental stress, proteins can potentially misfold or form clumps (aggregates). Such undesired protein waste can be toxic for cells and may even lead to cell death. Because several human neurodegenerative diseases are known to be linked to an accumulation of abnormal protein aggregates, basic science aimed to understand how cells remove cellular garbage is elementary for designing strategies for a potential prevention or cure of such disorders.
Scientists in the laboratory of Stefan Jentsch at the MPIB now successfully used baker’s yeast for screening for new cellular waste disposal pathways. Kefeng Lu, a postdoctoral researcher from China, discovered a new class of helper proteins (termed CUET proteins) present both in yeast and humans that recognize cellular garbage earmarked for disposal by an attached label in the form of the ubiquitously existing protein known as “ubiquitin”.
Importantly, these newly identified helper proteins channel the cellular garbage by a “self-eating” pathway (autophagy) to the lysosome, a compartment of cells dedicated for destruction and recycling. The Max Planck scientists could also show that a toxic protein related to the abnormal, aggregate-forming protein “huntingtin” of patients with the neurodegenerative Huntington’s disease is efficiently destroyed by the newly identified pathway. Remarkably, this pathway seems specific for aggregated proteins like huntingtin and appears to be more potent than previously discovered cellular garbage disposal mechanisms.
Because the identified cellular disposal mechanism operates in yeast as well, the researches will now take full advantage of its powerful experimental possibilities to investigate this pathway further.
A detailed analysis of this mechanism will be crucial to understand how aggregate-forming proteins lead to human diseases and may help to develop concepts for possible disease preventions.
K. Lu, I. Psakhye and S. Jentsch: Autophagic clearance of polyQ proteins mediated by the conserved CUET protein family. Cell, July 17, 2014.
Prof. Dr. Stefan Jentsch
Molecular Cell Biology
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Tel. +49 89 8578-2824
http://www.biochem.mpg.de/jentsch - Website of the Research Departement "Molecular Cell Biology" (Stefan Jentsch)
http://www.biochem.mpg.de/news/ueber_das_institut/forschungsbereiche/zellbiologi... - More press releases about the research of Stefan Jentsch
Anja Konschak | idw - Informationsdienst Wissenschaft
27.05.2015 | Okinawa Institute of Science and Technology (OIST) Graduate University
Seeing the action
27.05.2015 | University of California - Santa Barbara
The only professorship in Germany to date, one master's programme, one laboratory with worldwide unique equipment and the corresponding research results: The University of Würzburg is leading in the field of biofabrication.
Paul Dalton is presently the only professor of biofabrication in Germany. About a year ago, the Australian researcher relocated to the Würzburg department for...
Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.
Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...
Development and implementation of an advanced automobile parking navigation platform for parking services
To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...
The world's first electrical car and passenger ferry powered by batteries has entered service in Norway. The ferry only uses 150 kWh per route, which...
On Tuesday, 19 May 2015 the research icebreaker Polarstern will leave its home port in Bremerhaven, setting a course for the Arctic. Led by Dr Ilka Peeken from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) a team of 53 researchers from 11 countries will investigate the effects of climate change in the Arctic, from the surface ice floes down to the seafloor.
RV Polarstern will enter the sea-ice zone north of Spitsbergen. Covering two shallow regions on their way to deeper waters, the scientists on board will focus...
20.05.2015 | Event News
18.05.2015 | Event News
12.05.2015 | Event News
27.05.2015 | Power and Electrical Engineering
27.05.2015 | Health and Medicine
27.05.2015 | Physics and Astronomy