Discovered a new protein that intervenes in the sense of touch

The skin is the largest organ in the human body. A man’s can occupy two square meters, weigh up to five kilograms and be as thick as a centimeter, on the soles of the feet, or as thin as 0.5 millimeters, in the testicular sacs. It is the interface with which humans relate to the environment, feeling everything from cold to burns, through blows and shapes. In its three main layers, especially the epidermis, there are more than 11,000 proteins, most with functions to be discovered. Now, a group of researchers has discovered one, called ELKIN1, which seems to be essential in the sense of touch, the most forgotten of the senses. If we were missing, we might not be able to feel all the caresses.

Gary Lewin, from the Max Delbrück Center for Molecular Medicine (Berlin, Germany), has been researching ion channels, proteins present in the membrane, the envelope, of cells for more than 20 years. They have the ability to open and allow the exchange of ions between the inside and outside of the cell. They perform different functions depending on the cell type. In the case of sensory neurons, these channels convert a certain stimulus (heat, cold, pressure) into ionic currents (similar to electrical currents) that reach the most peripheral nerve endings to the brain. In 2020, studying melanoma tissues, a researcher from the Laboratory of Molecular Physiology of Somatic Sensations directed by Lewin discovered a protein that gave mechanical sensitivity to these cancer cells. “We discovered that they have ion channel activity very similar to that found in touch receptors. We identify ELKIN1 as responsible for this activity. The next step was obvious, to see if it had something to do with touch,” says the senior author of this research, who a few years ago discovered how shaved mice are insensitive to certain types of pain.

To verify this, they carried out a series of experiments with mice and human cells, the results of which have just been published in the journal Science. In the rodents, they modified the ELKIN1 gene using the CRISPR technique so that they did not express the functional protein. Then they tickled their hind legs with a cotton swab. They found that the unmodified ones removed them 90% of the time. However, the mutant mice only removed them 47.5% of the time, which showed that they had a loss of sensitivity to mechanical stimuli.

To carry out their experiments they had to design a new glass pipette capable of pressing neurons of a few microns.Felix Petermann, Max Delbrück Center

“ELKIN1 “It plays an important role in touch,” says Óscar Sánchez, from Lewin’s laboratory and co-author of the research. “But there are other ion channels, like PIEZO2. It is highly probable that in the cases in which ELKIN1 mutant mice showed a response to mechanical stimulation, PIEZO2 was compensating for the absence of the other channel,” he adds. In October 2021, the Nobel Prize in Medicine was awarded to researchers David Julius and Ardem Patapoutian. The first, for discovering temperature receptors. The second, for describing for the first time two channels in charge of feeling the pressure to those who called PIEZO1 y PIEZO2. One regulates the sensation of pressure in the internal organs, breathing or the control of urine in the bladder. The other, besides proprioception, the sense by which you can close your eyes and touch your nose, is key to the sense of touch. Now, if this work is confirmed, PIEZO2 y ELKIN1 they would work together.

For Lewin, “they perform complementary functions, each one represents approximately 50% of touch.” If so, the different tactile sensations from the outside would reach the endings of the sensory neurons that, starting from the spinal ganglia (in the spinal column), reach the epidermis. There, the channels PIEZO2 y ELKIN1in an overlapping way or in combination, they would convert the touch into an ionic current that would travel up through the nervous system until it reaches the brain, which is in charge of interpreting whether what you are feeling is a touch or a stone.

They needed to translate the results observed in mice to humans. To do this, they used a type of human sensory neurons obtained from stem cells that have electrophysiological properties similar to neurons in the spinal ganglia. In them, they detected both the presence of ELKIN1 as its contribution to the ionic currents triggered by the pressure applied with such small pipettes, just a few microns, which are one of the great novelties of this research.

If Lewin has been researching ion channels for 20 years, José Antonio Vega, professor of human anatomy and embryology at the University of Oviedo, has been researching mechanical stimuli for 43 years. “Since the beginning of this century, many of these channels have been known, the nociceptors (those for pain), thermoreceptors, those for extreme temperatures… the hygroceptors, that is, those for humidity that are there, but we have not discovered them yet. You have one arm out and the other in warm water. You perceive that it is wet, but we do not know how the sensation occurs. I have been behind them for years,” he says. Vega, who has had the opportunity to read the research of Lewin and his colleagues. It highlights his excellence, his high level. Even the technician. “I want to have that technology,” he says. But he also believes that they do not close the circle.

“They demonstrate that this gene is expressed in the mechanoreceptor sensory neurons of the spinal ganglia, ELKIN1. They also show that ELKIN1 “It is necessary and sufficient to confer mechanosensitivity to cell cultures,” highlights Vega, who adds: “They study the cells, they study the ganglia, they study the fibers, but they do not study the sensitive corpuscles that are under the skin.” For him, it is what is missing. in his book The touch. Touch and Feel (free access), of which Iván Suazo, from the Autonomous University of Chile, is also co-author, the anatomical and functional description of the sense of touch begins with a series of sensory organs present under the skin, the sensory corpuscles. That’s where it all begins. It is in them where mechanical pressure is converted into electrical stimuli through ion channels. “There is enough data to say that ELKIN1 It is involved in touch, but they do not show that it is in the place where the tactile sensation begins,” he concludes. Vega plans to ask the mice’s paws to look for the presence of the new ion channel in the corpuscles of their skin.

For Teresa Giráldez, professor at the University of La Laguna (Tenerife) and researcher of the different ion channels, this is the best of scientific research: “Work like this shows that the stories are not complete. People think, they gave Ardem the Nobel Prize [Patapoutian], there is nothing more to do. But you can always continue pulling the thread, as these researchers who propose this new mechanosensitive channel have done.” Like Vega, Giráldez points out what he misses: “What you have to demonstrate now is that the touch neurons read that gene, produce the protein and also express it in the membrane and produce the electrical stimulus.” Once they find it in the corpuscles themselves and, as happened with the 2021 Nobel Prize, they find people with the mutated ELKIN1 gene who do not differentiate, for example, a blow from a caress, they could win the prize.

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