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 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 >>>