Freiburg scientists explain the cell mechanism that transforms electrical signals into chemical ones
The enzymes nitric oxide (NO) synthase (NOS1) and protein kinase C (PKC) play an important role in a variety of signal transfer processes in neurons of the brain, as well as in many cell types of other organs.
Together with Prof. Dr. Bernd Fakler at the Institute of Physiology at the University of Freiburg, the scientists Dr. Cristina Constantin and Dr. Catrin Müller have shown for the first time that enzymes can be activated under physiological conditions through sole electrical stimulation of the cell membrane.
Protein super complexes that rapidly transform electrical signals at the cell membrane into chemical signal processes inside the cell emerge through direct structural interaction of both enzymes with voltage-gated calcium channels. The researchers have presented their work in the current issue of the scientific journal Proceedings of the National Academy of Sciences (PNAS).
The Fakler group has previously shown that both calcium-dependent enzymes NOS1 and PKC are components of the protein nano-environment of certain voltage-gated calcium channels (Cav2-channels) in the brain. As yet, however, it was not know how these enzymes communicate with the calcium channels.
The research group has now found that both enzymes are integrated into protein super complex with Cav2 channels. Within such Cav2-NOS1/PKC complexes NOS1 or PKC are anchored at the cytoplasmic side of the cell membrane and are placed at in the immediate vicinity of the channel pore.
Upon excitation of the cell membrane, the Cav2 channels open and deliver calcium ions to the cell cytoplasm, where they bind to both enzymes. Calcium binding activates the enzymes, which subsequently produce the diffusible second messengers NO or phosphorylate cytoplasmic target proteins.
Due to the proximity between channel and enzyme, electrical stimulations of less than a millisecond duration are required for effective electro-chemical coupling. The latter becomes maximal when the cell, instead of being stimulated by individual impulses, fires action potentials with a frequency of one hertz or more.
The Cav2-enzyme super complexes not only guarantee an ultrafast and reliable electro-chemical coupling. They also ensure that signal transduction remains locally restricted, that is, within an area less than a few nanometers around the Cav2 channels. This local restriction guarantees that the enzymes only initiate specific cellular processes, while other calcium signalling pathways, including cell death, are prevented.
In addition, the researchers’ experiments highlighted the physiological mechanism for activation of NOS1 and PKC thus presenting an alternative to the widely used synthetic activators, such as NO donors or diacylglycerols.
Bernd Fakler is the director of Department II of the Institute of Physiology and area coordinator of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies at the University of Freiburg.
Constantin, C.E., Müller, C.S., Leitner, M., Bildl, W., Schulte, U., Oliver, D., and Fakler, B. (2017). Identification of Cav2-PKC and Cav2-NOS1 complexes as entities for ultrafast electro-mechanical coupling. Proc Natl Acad Sci USA (in press).
Prof. Dr. Bernd Fakler
Institute of Physiology, Faculty of Medicine / BIOSS Centre for Biological Signalling Studies
University of Freiburg
Rudolf-Werner Dreier | Albert-Ludwigs-Universität Freiburg im Breisgau
Münster University chemists create new types of Lewis acids on the basis of phosphorus
22.10.2019 | Westfälische Wilhelms-Universität Münster
Obesity risk quantification:a jump towards the future through the artificial intelligence lens applied to lipid science
22.10.2019 | Technische Universität Dresden
Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.
Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...
A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)
It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
22.10.2019 | Materials Sciences
22.10.2019 | Medical Engineering
22.10.2019 | Power and Electrical Engineering