Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How enzymes communicate

19.05.2017

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.


Electro-chemical coupling through protein super complexes: The calcium channel (Cav2) delivers calcium ions (Ca2+) that activate the enzyme NO synthase (NOS) for generation of the messenger NO. Source: Bernd Fakler

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.

Originalpublikation:
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).

Contact:
Prof. Dr. Bernd Fakler
Institute of Physiology, Faculty of Medicine / BIOSS Centre for Biological Signalling Studies
University of Freiburg
Tel.: 0761/203-5175
E-Mail: bernd.fakler@physiologie.uni-freiburg.de

Weitere Informationen:

https://www.pr.uni-freiburg.de/pm-en/2017/how-enzymes-communicate?set_language=e...

Rudolf-Werner Dreier | Albert-Ludwigs-Universität Freiburg im Breisgau

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

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

Im Focus: Highly precise wiring in the Cerebral Cortex

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...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

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...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>