I have had a heavy load of homework the past few weeks, so I have not had a chance to post much. But I am back! I just presented a Nature article about vision at my department’s Journal Club, so I thought we would learn about the biochemistry of vision.
Let’s begin with the basics of vision:
The basic path that visual information follows is
- Optic chiasm
- Lateral geniculate nucleus (LGN) of the thalamus
- Visual cortex
- Various feedback routes
I am going to focus on the eyes- in particular, the cells that detect light and turn that information into electrical signals.
Those cells are found in the retina, shown here at the back of the eye.
Below is a drawing of the retina by my neuroscience hero, Santiago Ramon y Cajal.
Santiago Ramon y Cajal–not so beautiful, but awesome! I had this picture as my desktop background, but I think it scared my labmates 🙂
The cells that detect light are called photoreceptor cells, and they contain proteins called opsins. You have your rod and cone opsins; rods help you see in low light conditions, and cones help you see at normal light and distinguish color. Opsins are G-protein coupled receptors (GPCRs)–that is, they are receptors that cooperate with a certain protein, called a G-protein, to produce an effect when something activates the receptor.
The star of today’s post is retinal, a molecule that fits perfectly into a pocket in the opsin protein. Retinal changes structure when light hits it. This changes is called isomerization. Retinal is originally in the cis formation, and light causes it to isomerize to the trans formation. Its original form is called 11-cis retinal. Cis/trans isomerization is a way of describing the orientation of the functional groups in a molecule. As seen in the picture below, “rotation” occurs at a double bond, which is typical of cis/trans isomerization.
Cis means on the same side, while trans means on the opposite side. In cis retinal, the hydrogens are on the same side of the double bond. In the trans isomer, the hydrogen bonds are on either side of the double bond.
The reason why I put rotation in quotes earlier is that double bonds don’t rotate. When a photon of light hits cis-retinal, the double bond is broken, the rotation occurs, and then the double bond is reformed. Breaking and reforming double bonds requires energy, which the photon of light happily provides. This isomerization occurs in the span of a few PICOseconds. Sweet!
The change in retinal alters the shape of the molecule, from a bent formation to a straight-ish formation. When retinal changes, the opsin protein surrounding retinal is forced to shift its conformation. It’s like when you are cuddling with someone, and after a while you get uncomfortable. So you switch positions. But now your cuddling partner is uncomfortable. So they switch positions, too. Then you cuddle some more 🙂
So opsin shifts and shifts until it finally gets comfortable. The last conformational shift in opsin just so happens to bind especially well to G-protein. We talked about G-protein earlier; it is a separate protein that hangs out at the cell membrane near opsin. To continue our analogy, you and your cuddling partner finally get comfortable in your new position. But all that moving around woke the baby.
I would assume that the G-protein is randomly bumping up against opsin, but only sticks when opsin is in the new conformation. There are many types of G-proteins in the human body; the one discussed here is called transducin. Transducin normally is bound to GDP, or guanosine diphosphate. When transducin attaches to opsin, GDP is exchanged for a molecule of GTP, or guanosine triphosphate.
An interesting note here: one photon of light activates one opsin protein, but does not lead to to the recruitment of only one G-protein. Rather, each opsin protein recruits 10 G-proteins (not all at once, of course) in a process called signal amplification. Signal amplification is the specialty of GPCR’s. Without signal amplification, we would not be able to see as well, as the signals coming in to the brain would be very weak.
The replacement of GDP for GTP causes a subunit of transducin to break off and leave the retinal-opsin-transducin party that we have going on. This transducin subunit moves on to other proteins in the cell and continues sending the signal that light has hit the cell, much like runners in a relay race take turns carrying the baton from start to finish. In addition to passing on the signal, downstream players again amplify this signal 1000 times. From beginning to end, we have the signal from one photon of light amplified 10 x 1000= 10,000 times!
Eventually, the signal travels to the other side of the cell, where neurons wait for the signal. These neurons can then carry the message from the eye at the front of the head, past the optic chiasm, past the lateral geniculate nucleus, and finally to the visual cortex at the back of the brain.
Below are some websites that were especially helpful in understanding how light is turned into a signal that is sent to the brain:
If you are looking for more fun science, check out Ze Frank’s hilarious True Facts series on YouTube. Here is a sample: