Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Receptor provides a surprise

04.05.2015

Everything in life is based on the ability to perceive stimuli from the environment and to react to it. Receptors assume an important function. Now, while studying a specific class of receptors, scientists from the University of Würzburg have made an unexpected discovery.

A receptor sits in the cell wall and extends a kind of arm out. If a particular molecule or protein, such as a hormone or neurotransmitter, floats past, dissolved in the plasma, the receptor registers that with this arm and passes the information on to the cell interior. The cell can then react and, if necessary, initiate special steps. This is probably the mental image that many people, especially lay people, have when they think of a receptor.


Schematic representation of the effect of Latrophilin. The receptor modulates the perception of stimuli from the environment.

Scholz et al., Cell Reports (c) 2015 The Authors

Reaction to mechanical stimuli

But there is also another way: These receptors then respond to mechanical stimuli from the environment, such as vibrations, sound waves, or a stretch, and help organisms to hear, to perceive movements, and to control their own movements. Scientists from the University of Würzburg have now proven these abilities for a large class of receptors that had not been suspected of such properties previously. They report on their discovery online in the latest issue of the journal Cell Reports.

G-protein-coupled receptors, GPCRs for short, are the focus of the work performed by Dr. Tobias Langenhan and Dr. Robert Kittel. More specifically, their attention is directed at a special class of this receptor super-family, known as adhesion GPCRs. In a DFG research unit, for which Langenhan is the spokesperson, the two are examining the properties of these receptors together with scientists at the universities of Leipzig, Mainz, and Erlangen-Nuremberg, and the Amsterdam Medical Center of the University of Amsterdam. The research unit started work just under six months ago, and the first set of results are now available.

Key target for medication

“Hundreds of G-protein-coupled receptors are encoded in the human genome, and the way in which they work is now very well understood,” says Tobias Langenhan. One indication of their importance is the fact that around half of all clinically approved drugs target these receptors and, in doing so, treat ailments as varied as, for example, hypertension, asthma, and Parkinson’s disease. It is very different with adhesion GPCRs: although they are the second-largest class within the GPCR family, so far they are “poorly understood,” says Langenhan.

The research unit’s objective is to change that. And, the scientists have now been able to present an initial, surprising result to the public: “We were able to demonstrate that a special receptor from the group of adhesion GPCRs is involved in the perception of mechanosensory stimuli,” says Robert Kittel. Or, to put it another way, when organisms hear, perceive slight touch, or move, such GPCRs are also at play.

Behavioral changes in the fruit fly

In their study, the scientists focused on the larvae of the fruit fly Drosophila. “In these creatures we removed the very gene that encodes the receptor Latrophilin and replaced it with modified variants,” is how Langenhan explains the procedure. Next, the researchers observed the behavior of the larvae in as much detail as possible.

This revealed, for example, that larvae missing the receptor displayed a distinctive pattern of movement and covered shorter distances than the healthy control group. Instead of moving forwards in a purposeful manner, they just swung their heads over long phases. In a further experiment, the researchers took a more detailed look at special cells of the larval nervous system which are responsible for perceiving vibration stimuli. The finding there: larvae without Latrophilin receptors exhibited significantly weaker electrical responses than larvae that possess these receptors. A similar picture was found to do with hearing: Larvae without receptors required far louder signals for a flight reflex compared with healthy specimens.

A receptor as an amplifier

“Everything suggests, therefore, that these receptors register movements of the extracellular space in comparison with the cell and transmit this information to the cell interior,” is Robert Kittel’s summary of the results. Like a ship dropping anchor on the sea floor, adhesion GPCRs dock on surrounding structures and react if their “arm” is stretched or compressed.

What slightly complicates the work of the scientists here is the fact that in the case of receptors an “all-or-nothing principle” does not apply. “It is not the case that larvae missing Latrophilin are deaf and incapable of moving,” explains Tobias Langenhan. Instead, the receptors would intervene in the respective processes in a modulating manner, amplifying or cushioning them.

Good basis for further experiments

Robert Kittel and Tobias Langenhan believe that the results of this study represent a significant step on the road to classification of adhesion GPCRs. There are 33 varieties of them in the human body. There is much to suggest that there, too, they assume tasks similar to in fly larvae. For example, they can be found in hair cells in the inner ear. If they are missing or defective, the persons afflicted develop something known as “Usher syndrome,” a disease associated with early onset inner ear deafness or deafness from birth.

The new findings, in Langenhan’s words, are a good basis for now “developing further models and testing them in experiments.” After all, he says, there are still numerous unanswered questions in relation to receptors, such as how the signal is transported within the receptor and what “biochemical cascade” is triggered. Or why the receptor always breaks up into two parts during its creation, but appears reassembled at the cell membrane.

“We have now pulled the curtain to one side a little in an unexpected corner of physiology,” says Robert Kittel. For this reason both scientists are confident: “There is more to come!”

Personal profile

Since 2009, Robert Kittel has been running the Emmy Noether Group “Physiology and plasticity of the active zone in vivo” at the University of Würzburg’s Institute of Physiology.

Tobias Langenhan has been the group leader at the Department of Physiology (focus on neurophysiology) at the University of Würzburg since 2009 and head of the DFG research unit “Elucidation of Adhesion-GPCR Signaling” since October 2014.

Scholz et al., The Adhesion GPCR Latrophilin/CIRL Shapes Mechanosensation, Cell Reports (2015), http://dx.doi.org/10.1016/j.celrep.2015.04.008

Contact
Dr. Tobias Langenhan, MSc DPhil (Oxon), T: +49 (0)931 31-88681; tobias.langenhan@uni-wuerzburg.de

Dr. Robert J. Kittel, T: +49 (0)931 31-86046; Robert.Kittel@uni-wuerzburg.de

Gunnar Bartsch | Julius-Maximilians-Universität Würzburg
Further information:
http://www.uni-wuerzburg.de

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>