The skin is the largest organ in the human body. A man's testicle can be two square meters in size, weigh up to five kilograms and be up to one centimeter thick on the soles of the feet and up to 0.5 millimeters thick in the scrotum. It is the interface through which humans relate to the environment, feeling everything from cold to burns, through blows and shapes. In its three main layers, particularly the epidermis, there are more than 11,000 proteins, most with functions yet to be discovered. Now a group of researchers has discovered one called ELKIN1 that appears to be essential for touch, the most neglected sense. If we were missing, we might not be able to feel all the caresses.
Gary Lewin from the Max Delbrück Center for Molecular Medicine (Germany) has been researching ion channels, proteins that are present in the membrane of cells, for more than 20 years. They have the ability to open it and form pores that allow ion exchange between inside and outside. Depending on the cell type, they fulfill different functions. In the case of neurons, these channels convert a specific stimulus (heat, cold, pressure) into ion currents (similar to electrical currents) that reach the most peripheral nerve endings of the brain. In 2020, a researcher from the Molecular Physiology of Somatic Sensations Laboratory led by Lewin, while studying melanoma tissues, discovered a protein that provides mechanical sensitivity to these cancer cells. “We found that they have ion channel activity very similar to that of touch receptors. We identify ELKIN1 as responsible for this activity. The obvious next step was to find out if it had something to do with touch,” says the lead author of this research, who discovered a few years ago that shaved mice do not feel pain.
To check this, they conducted 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 changed the ELKIN1 gene using the CRISPR technique so that they did not express the protein of the same name. Then they tickled her hind legs with a cotton swab. They found that those that were not altered removed them 90% of the time (initially it was 100%). However, they only removed the mutant mice in 47.5% of cases.
To carry out their experiments, they had to design a new glass pipette that is capable of squeezing neurons of a few micrometers.Felix Petermann, Max Delbrück Center
“ELKIN1 plays an important role in touch,” says Óscar Sánchez from Lewin’s lab and co-author of the research. “But there are also other ion channels, like PIEZO2. It is likely that in the cases where the mice responded, this compensated 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 to discover temperature receptors. Second, to describe for the first time two people responsible for feeling the pressure, which they called PIEZO1 and PIEZO2. You regulate the feeling of pressure in the internal organs, breathing or controlling the urine in the bladder. The other sense, besides proprioception, the sense that allows you to close your eyes and touch your nose, is the key to the sense of touch. If this work is now confirmed, PIEZO2 and ELKIN1 would work together.
For Lewin, “they perform complementary functions, each one representing about 50% of the touch.” In this case, the different tactile sensations from the outside would reach the ends of the sensory neurons, which, starting from the dorsal root ganglia (in the spine), reach the epidermis. There, PIEZO2 and ELKIN1, overlapping or in combination, would convert touch into ionic current that travels up through the nervous system until it reaches the brain, which is responsible for interpreting whether what you are feeling is one touch or a stone.
They had to translate the results observed in mice to humans. To do this, they used a type of human sensory neuron derived from stem cells. They are not true nerve cells, but have the same electrophysiological properties as neurons in the dorsal root ganglia. In them they were able to detect both the presence of ELKIN1 and the currents triggered by pressure with such small pipettes, just a few micrometers in size, which represents one of the great novelties of this research.
While Lewis 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. “Many of these channels have been known since the beginning of this century, the nociceptors (those for pain), the thermoreceptors, those for extreme temperatures… the hygroceptors, that is, the ones for humidity, which exist, but we have not discovered them yet . You have one arm outstretched and the other in the warm water. They perceive that it is wet, but we do not know how the feeling arises. I’ve been behind them for years,” he comments. Vega, who had the opportunity to read the research of Lewis and his colleagues. His excellence and high level stand out. Even the technician. “I want to have this technology,” he says. But he also believes that the circle does not close.
“They show that this gene, ELKIN1, is expressed in the sensory mechanoreceptor neurons of the dorsal root ganglia. They also show that ELKIN1 is necessary and sufficient to confer mechanosensitivity to cell cultures,” emphasizes Vega, adding: “They examine the cells, they examine the ganglia, they examine the fibers, but they do not examine the sensitive bodies underneath. “the skin.” For him, it is what is missing. In his book The Touch. Touch and Feel (free access), co-authored by Iván Suazo from the Autonomous University of Chile, the anatomical and functional description of the sense of touch begins with a Series of sensory organs that are present under the skin, the sensory organs corpuscles. That's where it all starts. In them, mechanical pressure is converted into electrical stimuli via ion channels. “There is enough data to show that ELKIN1 is involved in touch, but they “We don't show that it is located where the tactile sensation begins,” he concludes. Vega wants to ask the mice's paws to look for the new ion channel in the blood cells in 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 have Ardem the Nobel Prize given [Patapoutian], there's nothing left to do. But you can keep pulling the thread, as these researchers have done who are proposing this new mechanosensitive channel.” Like Vega, Giráldez also points out what is missing: “What we have to show now is that the touch neurons read this gene , produce the protein and also express it in the membrane and generate the electrical stimulus.” Once they find it in the blood cells themselves and, as was the case with the 2021 Nobel Prize, find people with the mutated ELKIN1 gene, for example, a stroke can't distinguish it from a caress, they could win the prize.
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