Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers develop curious snapshot of powerful retinal pigment and its partners

01.03.2011
Three's not a crowd when it comes to triggering the senses and other physiological functions

Science fiction novelist and scholar Issac Asimov once said, "The most exciting phrase to hear in science, the one that heralds new discoveries, is not 'Eureka!' but 'That's funny.' " This recently rang true for an international team of researchers when they observed something they did not expect.

In a Journal of Biological Chemistry "Paper of the Week," the Berlin-based team reports that it has uncovered surprising new details about a key protein-protein interaction in the retina that contributes to the exquisite sensitivity of vision. Additionally, they say, the proteins involved represent the best-studied model of how other senses and countless other physiological functions are controlled.

"Nearly a thousand different types of these proteins are present in the human body, and nearly half of pharmaceutical drugs are targeted to them," explains Martha E. Sommer, a postdoctoral researcher at the Institute for Medicinal Physics and Biophysics at Charité Medical School and the first author on the JBC paper.

The retina, which is located at the back of the eye, is considered an outgrowth of the brain and is, thus, a part of the central nervous system. Embedded in the retina's 150 million rod-shaped photoreceptor cells are purplish pigment molecules called rhodopsin. It is the rhodopsin protein that is activated by the first glimmer – or photon – of light. Upon activation, the purple molecule binds another protein, known as transducin, to set off a cascade of biochemical reactions that ultimately results in vision.

"After this signaling event, rhodopsin must be shut off. This task is achieved by a third molecule called arrestin, which binds to light-activated rhodopsin and blocks further signaling," Sommer says. When rhodopsin is not properly shut off, overactive signaling can lead to a decrease in sensitivity to light and ultimately cell death. People who lack arrestin have a form of night blindness called Oguchi disease. "They are essentially blind in low light and can suffer retinal degeneration over time."

It is believed that the arrestin molecule silences rhodopsin's signaling by embracing it and elbowing out transducin.

"Since arrestin was first discovered more than 20 years ago, it was assumed that a single arrestin binds a single light-activated rhodopsin," Sommer says. "However, when the molecular structure of arrestin was solved using X-ray crystallography about 10 years ago, it was observed that arrestin is composed of two near-symmetrical parts – like an open clam shell."

The diameter of each side of the arrestin shell is about equal to that of one rhodopsin, she says, so some researchers wondered if a single arrestin might be able to bind to two rhodopsins.

It seemed like a simple enough question: To how many rhodopsins can a single arrestin bind? But, Sommer explains, little experimental work had been published about the topic, and the few studies that had been done seemed to support the one-arrestin-to-one-rhodopsin theory. That is, until now.

Using photoreceptor cells from cows, Sommer's team set out to shine a light on the rhodopsin-arrestin mystery once and for all. They exposed the rhodopsin molecules to low light and to bright light and managed to count how many arrestin molecules bound with them. In the end, it took three to tango.

"Increasing the light intensity increases the percentage of rhodopsins that are activated. Although the number of arrestins that bound per activated rhodopsin appeared to change with the percentage of activated rhodopsins -- with one-to-one binding in very low light and one-to-two binding in very bright light -- we hypothesize that arrestin always interacts with two rhodopsin molecules," Sommer says. "In low light, arrestin interacts with one active rhodopsin and with one inactive rhodopsin; whereas, in bright light, arrestin interacts with two active rhodopsins."

It's just a matter of probability, Sommer says: In brighter light, arrestin interacts with two activated receptors simply because there are more of them around.

"Although there were two fairly clear-cut theories regarding how arrestin binds rhodopsin, what was totally unexpected is that both can occur," she says.

But, what does this mean for the other senses and physiological functions controlled by other rhodopsin-like proteins? Rhodopsin is the most-studied member of the large family of G-protein coupled receptors, or GPCRs, and many well-known drugs target GPCRs. For example, when morphine binds to a GPCR, it affects the release of neurotransmitters in the brain and thus reduces pain signals. Meanwhile, beta-blockers, which are used to treat cardiac conditions and hypertension, block the activation of GPCRs by standing in the way of natural activating molecules.

"Nearly all GPCRs are normally bound by arrestin, and arrestin can greatly influence what happens to the GPCRs when they are acted on by drugs," says Sommer. "For example, many GPCR-targeted drugs become less effective with continued use. Part of this is because of arrestin. Arrestin binds to the activated GPCR and tells the cell to remove it from the cell surface. In other words, arrestin causes the cell to become less sensitive to the drug because it loses the receptors that normally catch the drug molecules."

By understanding how arrestin interacts with receptors like rhodopsin under healthy conditions, she says, researchers will be able to design better drugs that avoid such problems as desensitization.

Sommer made these discoveries with Professor Klaus Peter Hofmann and Martin Heck, both of the Institute for Medicinal Physics and Biophysics at the Charité Medical University. In 2007 the National Science Foundation awarded Sommer an international research fellowship that sponsored her move to Germany and subsequent collaborative research. The work was also funded by the German-based Deutsche Forschungsgemeinschaft, the largest research-funding organization in Europe.

The resulting "Paper of the Week" appears in the March 4 print issue of the Journal of Biological Chemistry.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions. For more information about ASBMB, visit www.asbmb.org.

Angela Hopp | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>