A telegraph key of touch
Before the invention of the telephone, telegraph lines were used to communicate over long distances. An operator pushed a key and interrupted an electrical current flowing through the line, allowing him to send information in pulses of Morse code. In a similar way, sensations of pain and pressure begin as electrical signals in the outlands of the nervous system. Here the telegraph operators are mechanosensory nerve cells that translate a mechanical force – such as a pinch – into an electric charge that can be routed to the brain. But how does the charge arise in the first place? Gary Lewin’s group has now discovered that sensory nerves are connected to their surroundings by a tether-like protein that seems to be acting as a sort of telegraph key. Their work appears in the Feb. 17 edition of the EMBO Journal.
An electron microscope image of a mechanosensory nerve cell (above) and a fibroblast (below). The cells are connected by molecular tethers (red arrow) that are needed to trigger sensations.
Normally the membrane around a cell acts as an insulator, blocking the flow of electrical charges between the cell interior and the environment. To generate an impulse this has to be overcome: the membranes contain ion channels made of proteins that open and allow charged particles to pass through. This creates a charge that initiates impulses that run immense distances along the membrane – more than a meter, for example, in the nerves that stretch from the feet to the spine. The current is switched off again when the channels close. So if you want to find the equivalent of a telegraph key for touch, Gary says, look for the mechanisms that open and close ion channels. But in mechanosensory cells these processes are poorly understood.
Studies of other types of nerves have provided two main hypotheses. In one model, the cell behaves like a sort of round, water-filled balloon with tiny holes in it. A force that directly pinches the surface of the balloon (the cell membrane) warps the shape of the holes (the channels) so that ions can slip through. Another idea is that force is transferred to the cell by rope-like proteins that tug on the membrane, opening and closing the channels. If you tied a string to the balloon and had someone try to pull it out of your hands, the surface would stretch and change the shape of nearby holes.
Researchers haven’t been sure which scenario applies to mechanosensory nerves, but the new study supports the second hypothesis. Using the electron microscope, post-doc Jing Hu, who now runs her own group in Tübingen, and other members of the lab discovered a tether-like molecule that links the membrane to its surroundings, a gluey mix of molecules called the extracellular matrix and skin cells such as fibroblasts. Movement and pressure in the matrix might pull on the tether, which would then act like the string tied to the balloon.
If this were true, the scientists reasoned, then you ought to be able to block a touch signal by cutting the tether. Gary’s lab has developed methods to grow the nerves in cell cultures and to measure the charge they produced. Jing Hu treated the cells with protein-cutting molecules and discovered that this shut off the signal.
“The loss and reappearance of mechanosensitive currents was always linked to the presence of this tether,” Gary says. “The cell only generates a charge when it’s there. Jing found the same thing when she did the experiment on intact skin nerves taken from mice. So this protein, which links the cell membrane to the matrix, has to be present to signal touch.”
Sensory cells produce different kinds of charges, and the effect was strongest on rapidly-adapting currents which flash along the nerves almost instantaneously after a very light touch. Gary says it makes sense to find that the telegraph key has a “mechanical” operator – the tether.
“Cells first notice that something is wrong through a change in pressure or some other physical force,” he says. “Our model shows how a force acting on the matrix and nearby cells can be transmitted to the nerve cell via the tether.”
To test the hypothesis, the scientists pulled on fibroblasts but not neighboring nerve cells with intact tethers. The nerves behaved exactly as if they had been jostled themselves, producing a strong electric current.
This work provides the first direct evidence, Gary says, that a tether is needed to produce sensations of touch. “Nearby nerves with other functions don’t have the protein,” he says. “Nor do they generate rapidly-adapting currents. When you eliminate the tether, you block signals in mechanosensory cells as well.” Finding this molecule, he says, gives his group a unique opportunity to unravel the molecular mechanisms that underlie touch.
- Russ Hodge
Highlight Reference:
Hu J, Chiang LY, Koch M, Lewin GR. Evidence for a protein tether involved in somatic touch. EMBO J. 2010 Feb 17;29(4):855 – 67.
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