Eyesight relies on light-sensitive cells called photoreceptors, which convert light into electric signals that are passed on to the brain. Two types of photoreceptors emerged during animal evolution: ciliary photoreceptors (cones and rods) in vertebrates and microvillar photoreceptors in many invertebrates. The mechanism of visual signal transduction (phototransduction) has been worked out in great detail for vertebrate photoreceptors. However, there are many unanswered questions in invertebrates. In particular, how light leads to the opening of ion channels that generate the electric signal is not understood. In an exciting study published recently in Science, Roger Hardie and Kristian Franze from the University of Cambridge, UK, examined the phototransduction mechanism in the eyes of Drosophila flies. What they found was most surprising: photoreceptor cells contract slightly in response to light. Hardie and Franze postulated that a mechanical force contributes to gating of the ion channels that produce an electrical signal.
The basic optical unit of the fly's compound eye is the ommatidium, which is made of eight photoreceptor cells. Densely packed microvilli (tubular membrane protrusions) in the photoreceptors – which harbour the visual pigment (rhodopsin) and associated signal transduction components – assemble to form light-guiding structures called rhabdomeres. It is known that light absorption activates rhodopsin, which triggers a signalling cascade that activates an enzyme known as phospholipase C (PLC). The activity of this enzyme, in turn, somehow activates the ion channels, known as TRP channels, but how this occurred was not clear.
Knowing that TRP channels in some other systems are mechanosensitive, Hardie and Franze came up with the brilliant idea of testing whether photoreception in Drosophila is connected with a mechanical force that might contribute to channel gating. To answer this question they performed stunning experiments using atomic force microscopy (AFM) to measure small changes in photoreceptor height by connecting the microscope's cantilever to the photoreceptor tip.
Intriguingly, when they exposed the eye to brief flashes of light they recorded quick contractions of the photoreceptor cells that were even visible through a conventional microscope. They also showed that the contractions were dependent on PLC activity, because they were eliminated in Drosophila mutants lacking a functional PLC. But how does photoreceptor contraction trigger TRP channels to open and produce a light-activated electrical signal?
Hardie and Franze hypothesized that the contractions are due to small changes in microvillar membrane tension, which are amplified because the microvilli are arranged in large stacks. PLC cleaves a lipid in the microvillar membrane, removing a bulky head group from the inner membrane, which could alter membrane tension, and this is detected in turn by TRP channels that open to generate an electric signal. To support this hypothesis, the duo inserted gramicidin, a well-known mechanosensitive ion channel, into the plasma membranes of isolated photoreceptor cells that lacked functioning TRP channels and measured the cells' electric activity. The modified photoreceptors responded electrically to light, indicating that gramicidin and TRP channels function in a similar mechanosensitive manner. Finally, the duo manipulated membrane stiffness with a range of compounds and solutions and found that that membrane tension is likely to be an essential factor in phototransduction.
Hardie and Franze have provided evidence that phototransduction in Drosophila eyes involves a mechanical force. Thus, changes in membrane tension appear to couple PLC activity to the opening of mechanosensitive TRP channels.
