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
Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy