Because misfolded proteins are often toxic, they are immediately refolded or degraded. Scientists of the Max Planck Institute (MPI) of Biochemistry in Martinsried near Munich have now shown in the yeast model that specific protein aggregates block an important degradation pathway for defective proteins – and thus disrupt the fragile molecular balance of the cell. The results of the study have now been published in the journal Cell.
PolyQ aggregates (red) inhibit degradation of misfolded protein (green) and accumulate cytosolic inclusions. The nucleus is stained in blue.
Picture: Sae-Hun Park, Copyright: MPI of Biochemistry.
Protein aggregates in cells can cause severe diseases such as Huntington’s disease. The massive movement disorders that appear with this disease are likely caused by aggregates of specific proteins, the polyQ proteins. Scientists of the research department “Cellular Biochemistry” headed by F.-Ulrich Hartl have now shown how these protein aggregates, commonly known as plaques, seriously disrupt cellular homeostasis.
Cells in the balance
The entire set of all cellular proteins is referred to as the proteome, whose composition is determined by a delicate balance of protein production and degradation. This process is regulated at several levels. Key helpers here are the molecular chaperones which aid the proteins in proper folding or lead them to degradation if the misfolding is irreparable. Among other things, this procedure serves to prevent the formation of protein plaques. Hartl’s team has now succeeded in demonstrating that polyQ aggregates in yeast primarily have an effect on the chaperone Sis1p.
This molecule functions as a cellular shuttle: It transports misfolded proteins from the cytosol into the cell nucleus, where they are degraded. The harmful polyQ plaques block this process by intercepting Sis1p. “As a result, misfolded proteins accumulate in the cell, which may contribute to the toxicity of polyQ aggregates,” said Sae-Hun Park, scientist at the MPI of Biochemistry and first author of the study.
Similar processes may occur in polyQ diseases in humans. Also in mammalian cells, misfolded proteins are transported from the cytosol into the nucleus. Here the chaperone DnajB1 plays a role similar to Sis1p in the yeast model. Contrary to prevailing opinion, Hartl’s team even assumes that this degradation pathway is the most important means of clearance of misfolded proteins from the cell interior. Further studies shall now show whether and to what extent these fundamental processes play a role in the pathogenic protein plaques.
Anja Konschak | Max-Planck-Institut
Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin
Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology