By now, everyone must be familiar with the inside out organization of the cephalopod eye relative to ours: they have photoreceptors that face towards the light, while we have photoreceptors that are facing away from the light. There are other important differences, though, some of which came out in a recent Nature podcast with Adam Rutherford (which you can listen to here), which was prompted by a recent publication on the structure of squid rhodopsin.
Superficially, squid eyes resemble ours. Both are simple camera eyes with a lens that projects an image onto a retina, but the major details of these eyes evolved independently — the last common ancestor probably had little more than a patch of light sensitive cells with an opsin-based photopigment. The general properties of this ancient eye can still be seen in modern eyes. They detect light with a simple molecule called retinal that is capable of absorbing a photon, changing its shape from the 11-cis form to the all trans form; basically, it flips from a chain with a kink to a straight chain. Retinal is imbedded in a protein called opsin. When retinal changes shape, it changes the shape of the opsin protein, too, which can then interact with other proteins in the cell membrane.
The next protein in the sequence is called a G protein. G proteins are ubiquitous intermediates for many cellular processes; when a receptor, like opsin, is activated, it activates a G protein, which then activates other proteins, starting a signaling cascade. In the podcast, I compare this to starting an avalanche. Opsin is an agent standing on a hill; when it receives a light signal, it nudges a small boulder (the G protein), which then tumbles down setting a whole series of rocks in motion. The G protein is an intermediate which takes a small change, the initial nudge, and amplifies it into the activation of many other proteins.
So far, this is all common to both cephalopods and vertebrates. We all have retinal bound to an opsin which activates a G protein which starts a series of events that lead to a change in electrical activity in the photoreceptor cell. Now here are the differences.
We vertebrates have ciliary photoreceptors which use a variant of the opsin protein called c-opsin. The c-opsin activates a G protein called Gt, which activates an enzyme called phosphodiesterase, which decreases the concentration of a messenger molecule called cyclic GMP. This cGMP binds to sodium channels and opens them; decreasing levels turns off the electrical activity of the cell. Our photoreceptors are most active when it is dark, and when it is light, they reduce their level of electrical activity. One way to think of it is to imagine the photoreceptors being able to say only one thing to the rest of the retina and brain: “It’s dark!” When it is dark, all the photoreceptors are constantly shouting that message back; when it’s light, the photoreceptors go quiet. The retina integrates this information to put together a picture of light and dark areas in the visual field.
Cephalopods use a different pathway. They have rhabodmeric photoreceptors that use a version of opsin called r-opsin. R-opsin binds a different G protein, called Gq. Gq activates the phosphoinositol pathway, which uses diacylglycerol as a messenger, which opens ion channels in the membrane, exciting the cell. Squid photoreceptors can send the message “It’s light!”, and they shout it back when the lights are on, and go quiet when it’s dark. Logically, this is equivalent to what the vertebrate eye does, it’s just that the polarity is reversed. We have an electrical switch installed that you flip down to send a signal back, while squid have a switch that you flip up.
This difference is entirely arbitrary! We have some cells that use Gq, too, just not for photoreception; similarly, invertebrates have c-opsins and Gt proteins. Some cells even combine both kinds of pathways, which is a clever way to get double-duty out of a single cell — they can respond one way to one kind of signal, and in a diferent way to a different kind of signal. What this represents is an accident of evolution, that 600 million years ago the progenitor of the lineage that led to us settled on c-opsin/Gt for its photoreceptors, while the ancestor of squid used an r-opsin/Gq combo for the same job.
What triggered this bit of background and the Nature podcast is a new paper by Murakami and Kouyama in which they’ve worked out the structure of squid opsin. This is significant because it shows us both the similarities and differences between a c-opsin and an r-opsin, and allows us to look in more detail at the biophysics of light transduction in invertebrates. Here is that structure, with squid r-opsin overlaid in brown over blue bovine c-opsin.
The first thing to notice is the overall similarity: both have the same general structure, with seven helices spanning the membrane and forming an internal pocket for retinal. There are subtle differences in the conformation, with the squid opsin apparently having a slightly roomier retinal pocket, for instance, but in general the similarities are obvious. Keep in mind that these proteins are separated by over half a billion years of evolution!
The most obvious difference is at the top of the diagram, on the cytoplasmic side of the membrane, where two of the helices (V and VI) have formed a protrusion in the squid that is not present in the cow. This is the binding site for the Gq protein, and where all the specific differences in the signaling cascades triggered by the two proteins arises — one small bump.
Of course, this is all important to know for better understanding the eye of the squid, but some of the more selfish among you may be wondering what this can possibly do to benefit humankind. We don’t know. However, one possible human interest angle is that our homologous r-opsin protein is called melanopsin, which is a molecule we use for regulating our circadian rhythms. Understanding the structure of r-opsin may someday help in drug design for treating sleep disorders, for instance.
I think it’s enough to know more about cephalopods, myself.
Murakami M, Kouyama T (2008) Crystal structure of squid rhodopsin. Nature 453(7193):363-369.