Heidelberg researchers characterise a mostly unknown yeast protease – an enzyme playing a major role in transporting nutrients
Heidelberg researchers have gained new insights on the function of a presenilin-related protein in the model organism baker’s yeast with regard to the regulation of the cells’ nutrient supply: This membrane protein is a protease called Ypf1.
It regulates the amount of nutrient transporters making it to the cell surface and controls the absorption of nutrients from the cell’s environment as could be shown by the researchers around Dr. Marius Lemberg of Heidelberg University’s Center for Molecular Biology.
In humans, the related presenilin-1 gene, when mutated, is one of the factors which lead to a hereditary early-onset and severe form of Alzheimer’s disease, as Dr. Lemberg says. The scientist collaborated with colleagues in Rehovot, Munich and Freiburg. Their results were published in the journal “Molecular Cell”.
When Dr. Lemberg's team started its work it was only known that Ypf1 belongs to an unusual class of membrane proteases. These proteases are enzymes that are able to cleave peptide chains within cellular membranes. However, despite massive knowledge from yeast genetics as well as recently developed biochemical assays, Ypf1’s function in this process remained in the dark.
“Since proteases like Ypf1 are working at the crossroads of essential cellular processes, their physiological tasks and the study of their substrates are an important research field,” says Dr. Lemberg, who closely collaborated with Dr. Maya Schuldiner of the Weizmann Institute of Science in Rehovot (Israel).
The breakthrough in understanding Ypf1 came with quantitative studies of the proteome, i.e. all the proteins in the cell. In the course of these experiments the researchers observed that in the absence of the Ypf1 protease, a high-affinity zinc transporter accumulates in individual fractions of the cell membrane.
Moreover, with the help of systematic approaches the researchers were able to demonstrate that Ypf1 generally regulates how many of these nutrient transporters reach the cell surface. Thus, the protease controls the way in which nutrients are being taken up from the environment. The molecular biologists also proved that Ypf1 cooperates directly with components of the so-called ER-associated degradation pathway (ERAD) to dispose of surplus transporter proteins.
According to Dr. Lemberg, the Ypf1 protease also enables yeast cells to “sense” changes in the nutrition level and to react when the supply of nutrients declines and limitations of cell functions are imminent. The reduction of transporters is then being suspended. “The Ypf1 protease allows yeast cells to prepare themselves for starvation.
This process is as important for unicellular organisms as a functional brain is for animals,” emphasises the Heidelberg researcher. As Dr. Lemberg says, these new insights form the basis for a molecular understanding of how cells control the composition of their membranes. The scientists hope to be also able to draw conclusions about the origin of human diseases, such as the hereditary early-onset form of Alzheimer’s.
The research group of Dr. Lemberg is a member of the DKFZ-ZMBH Alliance, the strategic collaboration between the German Cancer Research Center (DKFZ) and the Center for Molecular Biology of Heidelberg University (ZMBH). The research was funded in the framework of the Network Aging Research of the Baden-Württemberg Foundation as well as the university’s Collaborative Research Centre “Cellular Surveillance and Damage Response” (CRC 1036). In addition to the research team of Dr. Schuldiner, scientists of the German Center for Neurodegenerative Diseases in Munich and of the University of Freiburg have significantly contributed to this project.
D. Avci, S. Fuchs, B. Schrul, A. Fukumori, M. Breker, I. Frumkin, C. Chen, M.L. Biniossek, E. Kremmer, O. Schilling, H. Steiner, M. Schuldiner and M.K. Lemberg (2014) The Yeast ER-Intramembrane Protease Ypf1 Refines Nutrient Sensing by Regulating Transporter Abundance. Molecular Cell 56, 630-640 (4 December 2014), doi:10.1016/j.molcel.2014.10.012
Dr. Marius Lemberg
Center for Molecular Biology of Heidelberg University
Phone: +49 6221 54-5889
Communications and Marketing
Press Office, phone: +49 6221 54-2311
Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences