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
Signaling Pathways to the Nucleus
19.03.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
In monogamous species, a compatible partner is more important than an ornamented one
19.03.2018 | Max-Planck-Institut für Ornithologie
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
19.03.2018 | Physics and Astronomy
19.03.2018 | Materials Sciences
19.03.2018 | Event News