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!”
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
Dr. Tobias Langenhan, MSc DPhil (Oxon), T: +49 (0)931 31-88681; firstname.lastname@example.org
Dr. Robert J. Kittel, T: +49 (0)931 31-86046; Robert.Kittel@uni-wuerzburg.de
Gunnar Bartsch | Julius-Maximilians-Universität Würzburg
New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington
Breakthrough in Mapping Nicotine Addiction Could Help Researchers Improve Treatment
04.10.2016 | UT Southwestern Medical Center
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
20.10.2016 | Physics and Astronomy
20.10.2016 | Physics and Astronomy
20.10.2016 | Physics and Astronomy