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Opsins: Not Just for Eyes

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Science  15 Feb 2013:
Vol. 339, Issue 6121, pp. 754-755
DOI: 10.1126/science.339.6121.754

Studies in invertebrates are enriching our sense of how versatile and ancient these light-sensitive proteins are.

Light sensors.

Opsin-laden photoreceptor cells (green, red) provide juvenile sea urchins a means to detect light.

CREDIT: MARIA INA ARNONE/STAZIONE ZOOLOGICA ANTON DOHRN

When researchers got their first glimpse of the sea urchin genome in 2006, they were surprised to find genes for opsins, light-sensitive proteins without which vision as we know it today would be impossible. Living in the subtidal zones, sea urchins are not only eyeless, but also headless, and, ostensibly brainless. They seemed to lack the specialized photoreceptor cells that house opsins in the eyes of other animals. "Nobody knew what [the opsins] were for," recalls Maria Ina Arnone, a developmental biologist who has long studied sea urchins at the Stazione Zoologica Anton Dohrn in Naples, Italy, one of the world's oldest marine labs.

Arnone's preliminary analyses suggested an opsin gene was active at the base of the tube feet, the tiny projections located in and around urchin spines. And in 2011, her group showed that these tube feet were loaded with photoreceptor cells that had been missed because they lack pigment typically associated with opsins.

That work and other recent studies have driven home the fact that a wide variety of organisms don't need traditional eyes to make use of opsins, and that opsins can likely sense more than light. Last month, at the annual meeting of the Society for Integrative and Comparative Biology (SICB) in San Francisco, Arnone and other researchers revealed the rich history and unexpectedly broad utility of these proteins. In fruit flies, for example, they may be involved in hearing. "Opsins can be expressed in many more tissues than the simple eye," Arnone says.

Beyond eyes

Hints that opsins existed outside the eye started dribbling in almost 25 years ago, with suggestions that fish skin and dove brains contained the molecules. Among the first to pin down an extraocular opsin protein were Ignacio Provencio and Mark Rollag at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and their colleagues. They knew that pigment cells in amphibian skin reacted to light and eventually isolated an opsin in frog skin that they named melanopsin in 1998. Until then, researchers thought there was one kind of opsin in vertebrates, called ciliary opsin, and another, more ancient kind, rhabdomeric opsin, in invertebrates. But though melanopsin was found in a frog, it looked more like the invertebrate opsin.

Provencio and Rollag also found melanopsin in the frog eye and brain and over the next few years, a flurry of papers teased out which other vertebrates possess the protein and provided clues to melanopsin's function. Researchers have found it in mouse and human neural tissue, for example, and in some animals, it helps establish circadian rhythms (Science, 20 December 2002, p. 2297).

Melanopsin hinted at an underappreciated complexity of opsins. And a 2003 survey of opsins throughout the animal kingdom by Detlev Arendt from the European Molecular Biology Laboratory in Heidelberg, Germany, drove home that both rhabdomeric and ciliary opsins are ancient and that the invertebrate/vertebrate divide for these types doesn't hold up. But the search for opsins in animals other than vertebrates and insects and in places other than eyes didn't really take off until recent advances in DNA sequencing made it possible to probe the genomes of a wide variety of organisms, such as the sea urchin.

Arnone has slowly homed in on how opsins help this simple creature use light and "see." These spiny echinoderms tend to avoid direct sunshine. Some will cover themselves with debris; others move under rocks in search of shadow. Researchers have shown some that sea urchins can even distinguish different shaped objects. Last month at the SICB meeting, Arnone proposed that the opsin photoreceptor cells in the sea urchin are positioned at the base of the tube feet such that they lie partially in the shadow of its calcite skeleton, allowing the skeleton to serve the same purpose as pigment in typical eyes—most opsins co-occur with pigment, which shields part of a photoreceptor cell so it can register the direction of incoming light. She has also shown that the photoreceptor cells connect to the five radial nerves in the brainless urchin, which may enable the input from the different photoreceptor cells to be compiled, much like an insect's compound eye does.

In echinoderms, the opsin story is complex. The opsin at the base of the tube feet is the rhabdomeric type, and Arnone has also found this version in microscopic light-sensitive "eyes" located at the tips of starfish arms. At the meeting, she described a second, ciliary opsin in the tips of urchin tube feet, in urchin skin, and possibly in its muscles. It's also present in their larvae, she said. Arnone is not sure what this ciliary opsin does. But because echinoderms, which include starfish and sea urchins, sit at the base of the deuterostomes, the animal group that includes vertebrates, both types of opsins were likely already present in the earliest deuterostomes. How the different opsins later became specialized for use in vision remains a mystery, she notes.

Opsins everywhere

Opsins galore.

Opsins have been discovered in eyeless chitons, comb jellies and hydra, and in the skin of octopus (clockwise from top).

CREDITS (CLOCKWISE FROM TOP LEFT): DANIEL SPEISER/UNIVERSITY OF CALIFORNIA, SANTA BARBARA; WILLIAM BROWNE/UNIVERSITY OF MIAMI; DAVID PLACHETZKI/UNIVERSITY OF CALIFORNIA, DAVIS; MARKOS A. ALEXANDROU/UNIVERSITY OF CALIFORNIA, SANTA BARBARA

After opsins were found in sea urchins, evolutionary biologist Todd Oakley from the University of California (UC), Santa Barbara, wondered where else they might be. He and his colleagues started looking even closer to the base of the animal tree of life for these proteins. In 2007, Oakley recalls, "that led us to Cnidaria," the group of animals, including hydra and jellyfish, characterized by specialized cells that fire venom-equipped barbs that sting prey or deter predators. His group found opsins in cells associated with cnidarian stinging cells, and in the 5 March 2012 issue of BMC Biology they reported that stinging cells were less likely to fire in bright light. "Even though [stinging cells] had been studied for decades, there were very few hints that light was involved in firing," Oakley says. The prevailing wisdom was that chemicals in the water influenced firing. But here was a light-sensing role for opsins that did not involve image generation or true vision.

His team has now found that opsins have a similar sway over the firing of stinging cells in several distant cnidarian relatives—two anemone species and moon jelly polyps—suggesting that this nonvisual role for opsins is ancient. "It may be that [a] role in vision came later," suggests Craig Montell, a neurobiologist who recently moved to UC Santa Barbara.

At the San Francisco meeting, David Plachetzki from UC Davis reported that the hydra's opsin-laden cells near the stinging cells also contain taste receptors. That leads Plachetzki to propose that the ancestor to specialized photoreceptor cells was a cell that responded to several types of stimuli.

Supporting evidence for that scenario comes from other work. Desmond Ramirez in Oakley's lab reported finding opsins in the cilia of octopus skin, which are already known to be sensitive to mechanical stimuli. "So it's potentially another case where there is multimodal sensation," Oakley says. And his postdoc Daniel Speiser found opsins in small sensory tentacles extending from the shell plates of mollusks called chitons. Whether these proteins are involved in mechanosensing or light-sensing is still to be determined.

Probing even deeper down the animal tree of life, Christine Schnitzler from the National Human Genome Research Institute in Bethesda has found three strange-looking opsin genes in the recently completed genome of the comb jelly Mnemiopsis leidyi. Comb jellies are considered by many to be among the first multicellular animals to arise. Two comb jelly opsins loosely resemble the rhabdomeric and ciliary opsins, while a third looks like neither, Schnitzler reported at SICB. The proteins show up in two parts of the animal's gelatinous body—in a sensory organ opposite the comb jelly's mouth that helps the creature stay oriented in the water and in the cells that generate bioluminescence. Because the opsins in those cells are sensitive to the same wavelength as the light given off, they may be used by the animal to sense and control how much it's glowing, Schnitzler proposed at the meeting.

Other roles

Even in animals with eyes, researchers are finding they have more to learn about opsins. These proteins have been long studied in eyes of the fruit fly Drosophila melanogaster, but Martin Göpfert from the University of Göttingen in Germany has now come across them in the insect's antennal ear. His team had been screening for insect ear genes to try to find genes that might be involved in human hearing loss. They looked for genes that were more active in normal fruit flies than in mutant fruit flies lacking the antennal ear. Among the 275 upregulated genes identified were four genes for opsins previously found expressed only in the fly's eyes.

These four genes are also expressed in the mechanosensory cells of the ear and are required for hearing, the Göpfert team reported in the 31 August 2012 issue of Cell. "Finding that these cells use opsins for mechanosensation suggests that these proteins may have already served sensory roles before photoreceptors have evolved," Göpfert says. "In the ear, opsin function seems light-independent."

Montell's group has identified what may be another nonvisual role for opsins: temperature sensation. Drosophila larvae prefer 18°C, seeking it out over subtly different temperatures, such as 19° to 24°C. In trying to find the temperature sensor, "we weren't expecting opsin to be important," Montell recalls. But in 2011, Montell and his colleagues discovered that mutant flies lacking the visual opsin ninaE no longer showed this preference. When the researchers put a mouse melanopsin gene into the mutant fruit flies, the larvae oriented to 18°C (Science, 11 March 2011, p. 1333). Fruit flies have seven opsins, and Montell says that still unpublished work from his lab establishes nonlight-sensing roles for five of them.

Montell predicts that researchers are just beginning to appreciate all that opsins can do. Arnone agrees. When she first looked at opsins 6 years ago, the project was very much a sideline effort. But, aided by a new grant to study the proteins, she expects that opsin research will grow to take up half her lab. In the next year, Montell says, "there will be a lot more to talk about."

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