Scientists at the University of Konstanz reveal molecular control of protein transport in cells / Publication in “Science”
A package arriving at the wrong address causes confusion, in many cases leading to stress. This concept also applies to protein transport in living cells. The team around the Konstanz-based biologist Professor Elke Deuerling, who also is the speaker for the Collaborative Research Centre “Chemical and Biological Principles of Cellular Proteostasis” (SFB 969), has now discovered exactly what is necessary to prevent erroneous protein transport.
Two competing activities ensure that proteins safely arrive at their intended destination – in cell organelles like the mitochondria and the endoplasmic reticulum (ER), in particular. The team succeeded in uncovering that, in contrast to the prevailing view, successful protein transport requires not only the signal recognition particle (SRP), but also the nascent polypeptide-associated complex (NAC). The elucidation of this fundamental cellular process may have far-reaching implications for research on age-related defects and diseases, such as Alzheimer’s. The study’s results were published 10 April 2015 in “Science.”
In 1999, Günter Blobel was awarded the Nobel Prize for Medicine for the discovery of the signal recognition particle (SRP) pathway that sorts and delivers proteins to the ER. Within the SFB 969, Dr. Martin Gamerdinger now was able to prove that also the protein complex NAC is necessary for accurate protein sorting by inhibiting the transport of non-authentic proteins into the ER. “Until now,” states Martin Gamerdinger, “it was generally believed that solely the signal recognition particle fulfills the critical role in correct protein transport by stimulating the process. We discovered, however, that the process also must be inhibited in order to prevent erroneous protein targeting.” Evidence for this antagonistic principle was collected with the help of an experimental set-up using the nematode C. elegans and reducing the level of NAC. Martin Gamerdinger comments: “We observed, that in the absence of NAC, the animals experience stress in the ER as well as in mitochondria and live only half as long.”
Elke Deuerling compares NAC with ticket checkers who let people into football games, concerts or the cinema based on the kind of ticket. This controlling function is crucial because ribosomes that produce proteins tend to bind the membrane of the endoplasmic reticulum unspecifically. Without NAC, a part of the proteins being produced by ribosomes mistakenly end up in the ER. “NAC acts as a shield between the ribosome and the endoplasmic reticulum. Only once a protein leaves the ribosome with the right signal or “ticket” for the ER, the signal recognition particle appears to push aside the NAC complex and the protein can enter the ER. The transport only correctly works when the balance between SRP and the NAC complex is right,” explains Elke Deuerling.
Proteins ending up in the wrong location, not only disturb the homeostasis in the endoplasmic reticulum, but also in mitochondria, because proteins specific to them don’t arrive in the mitochondria, but rather in the endoplasmic reticulum. “This creates an enormous stress in the organism and leads to a drastically shortened lifespan of C. elegans,” says the molecular biologist.
The protein complex NAC is essential for all higher cells, also in humans. For this reason, it was impossible to “turn off” the NAC genes, since this would lead to immediate cell death. Instead of the “knock-out” method, Martin Gamerdinger utilized the “knock-down” principle by simply reducing the NAC levels. Elke Deuerling adds: “The trick was to choose the right model organism, C. elegans. We were able to achieve our results by combining a variety of scientific techniques - biochemical approaches, the establishment of new transgenic C. elegans strains and high-resolution microscopy – and with the additional support of my doctoral student Anne Hanebuth and the applied bioinformatics Junior Professor Tancred Frickey.”
Martin Gamerdinger, Marie Anne Hanebuth, Tancred Frickey, Elke Deuerling: “The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum”. In: Science, 10. April 2015, Issue 34, No. 6231.
University of Konstanz
Communications and Marketing
Phone: +49 7531 88-3603
Prof. Elke Deuerling
University of Konstanz
Phone: +49 7531 88-2647
Julia Wandt | idw - Informationsdienst Wissenschaft
International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine
New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Power and Electrical Engineering
24.10.2016 | Life Sciences
24.10.2016 | Life Sciences