Visual pigment rhodopsin forms two-molecule complexes in vivo

July 25, 2016

The study of rhodopsin—the molecule that allows the eye to detect dim light—has a long and well-recognized history of more than 100 years. Nevertheless, there is still controversy about the structure in which the molecule exists in the cells of the eye. In a paper published today in the Proceedings of the National Academy of Sciences, researchers at Baylor College of Medicine, the University of Utah and the Johns Hopkins University School of Medicine have determined for the first time the most likely configuration of rhodopsin in a living organism, and hope this discovery will help develop future therapies for retinitis pigmentosa, a degenerative eye disease for which there is no known cure.

"Until recently, the established concept, based on a vast amount of literature from biochemistry, biophysics and physiology, sustained that exists and functions as a monomer—a single molecule. About 10 years ago, however, evidence began to emerge that rhodopsin may exist as a dimer, a two-molecule complex. Nonetheless, all of the supporting evidence available is from in vitro experiments, that is, experiments performed outside of a living organism," said senior author Dr. Yingbin Fu, associate professor and Sarah Campbell Blaffer endowed chair of ophthalmology at Baylor. "In this study we have shown, for the first time in vivo—inside a living organism—that rhodopsin exists as a dimer."

The structure and function of rhodopsin have long served as a model for G-protein-coupled receptors (GPCRs), which constitute the largest family of protein molecules that allow the cell to sense the outside environment, including light, odors and hormones.

Many GPCRs have multiple subunits that are different from each other. Rhodopsin, on the other hand, has one subunit, thus making it difficult to distinguish rhodopsin monomers from rhodopsin dimers, in vivo. To determine whether rhodopsin forms monomers or dimers in vivo, the researchers tested rhodopsin's ability to form dimers with a different molecule, a cone opsin.

"We obtained the first clear in vivo evidence by taking advantage of a unique genetically modified mouse line that expresses a cone opsin, a molecule responsible for color vision, in rods—the cells responsible for dim light detection that naturally express rhodopsin," said Fu. "We found that in the absence of a vitamin-A based chromophore, a condition required for this experiment, the cone opsin can mature and target to the right place if and only if rhodopsin is present to help it along, that is, when cone opsin and rhodopsin form a two-molecule complex."

Most importantly, the researchers also determined which sections or domains of the rhodopsin molecule were essential for forming dimers. "We have also confirmed a domain that is key for rhodopsin dimerization and shown, again in vivo, that rhodopsin maturation and targeting to its right place on the cell becomes defective when dimerization is disrupted by blocking the domains involved in forming dimers."

The authors hope that their findings will also help develop future treatments for , which has been associated with more than 100 mutations of rhodopsin. "It is conceivable that some of the mutations that cause retinitis pigmentosa may affect the process of rhodopsin dimerization. When developing future therapies for this condition, it is important to keep in mind that rhodopsin works as a dimer," said Fu.

"Considering that rhodopsin is the prototypical GPCR, that the evidence for a functional rhodopsin monomer is so strong, and that strong general resistance remains in the field against the rhodopsin-dimer concept, our in vivo experiments reported here are therefore crucial for steering the field in the correct direction," said co-author Dr. King-Wai Yau, professor of neuroscience at Johns Hopkins University.

"As a clinician involved in multiple clinical trials of treatment for retinitis pigmentosa, I can say this is a very important finding," said Dr. Timothy Stout, chair and professor of ophthalmology and director of the Cullen Eye Institute at Baylor. "We recruited Dr. Fu in September 2015 as a member of the new Center for Retinal Research at Baylor. This work is another demonstration of Dr. Fu's innovative approaches and multidisciplinary expertise for studying retina diseases. I am confident that Dr. Fu's team will continue to make great discoveries in retinal research."

Explore further: Shedding light on the evolution of whale vision

More information: Dimerization of visual pigments in vivo, Proceedings of the National Academy of Sciences, www.pnas.org/cgi/doi/10.1073/pnas.1609018113

Related Stories

Shedding light on the evolution of whale vision

February 20, 2016
Eyes are the window between an animal and its environment, and if your environment has changed as much as a whale's has over the last 50 million years, they tell an intriguing story about your evolutionary history. As marine ...

Why animals don't have infrared vision

June 9, 2011
On rare occasion, the light-sensing photoreceptor cells in the eye misfire and signal to the brain as if they have captured photons, when in reality they haven't. For years this phenomenon remained a mystery. Reporting in ...

Crag keeps the light 'fantastic' for photoreceptors

December 4, 2012
The ability of the eye of a fruit fly (Drosophila melanogaster) to respond to light depends on a delicate ballet that keeps the supply of light sensors called rhodopsin constant as photoreceptors turn on and off in response ...

Recommended for you

Study reveals breakthrough in decoding brain function

September 25, 2017
If there's a final frontier in understanding the human body, it's definitely not the pinky. It's the brain.

Overturning widely held ideas: Visual attention drawn to meaning, not what stands out

September 25, 2017
Our visual attention is drawn to parts of a scene that have meaning, rather than to those that are salient or "stick out," according to new research from the Center for Mind and Brain at the University of California, Davis. ...

A brain system that builds confidence in what we see, hear and touch

September 25, 2017
A series of experiments at EPFL provide conclusive evidence that the brain uses a single mechanism (supramodality) to estimate confidence in different senses such as audition, touch, or vision. The study is published in the ...

Brain guides body much sooner than previously believed

September 25, 2017
The brain plays an active and essential role much earlier than previously thought, according to new research from Tufts University scientists which shows that long before movement or other behaviors occur, the brain of an ...

The rat race is over: New livestock model for stroke could speed discovery

September 25, 2017
It is well-known in the medical field that the pig brain shares certain physiological and anatomical similarities with the human brain. So similar are the two that researchers at the University of Georgia's Regenerative Bioscience ...

Touching helps build the sexual brain

September 21, 2017
Hormones or sexual experience? Which of these is crucial for the onset of puberty? It seems that when rats are touched on their genitals, their brain changes and puberty accelerates. In a new study publishing September 21 ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.