Compared to their knowledge of other senses, scientists know relatively little about how cells sense touch. A newly confirmed family of mechanosensors, comprising more than a dozen members and present in both plants and animals, is an important step toward a better understanding. The protein family, called OSCA in plants and TMEM63 in animals, was described in a recent eLife study.
“Mechanical forces are everywhere,” says Ching Kung, an emeritus professor who worked in mechanosensitivity at the University of Wisconsin–Madison. For example, plant roots must sense rocks in the soil to go around them, and many animals rely on mechanosensation to measure their own blood pressure. These sensors are also important in disease; for example, a mechanosensor called Piezo2 has been linked to human diseases with symptoms including insensitivity to light touch. (See Inner Workings: Unlocking the molecular mechanisms behind our sense of touch) “These findings broaden our horizon and promise deep understanding that is relevant to human physiology and pathology,” says Kung, who was not involved with the new study.
Known mechanosensors convert force into a current of positive ions flowing into a cell. Researchers in the lab of Ardem Patapoutian, at Scripps Research in La Jolla, California, were interested in plant genes in the 15-strong OSCA family. Defects in these genes stunt plant growth under high salt conditions, suggesting they respond to osmotic pressure. But Patapoutian’s team wondered if the OSCA proteins were responding not directly to the osmotic pressure, but to the tension on the cell’s plasma membrane as the cells, withering in salt solution, stretched away from their points of contact with the surrounding cell wall.
To test the ability of OSCAs to sense membrane stress and movement, they sought to express them in a cell type incapable of sensing any such external pressure. So they generated human kidney cultures lacking mechanosensation.
Postdoc Swethy Murthy borrowed OSCA genes from the mustard Arabidopsis thaliana and put them in the kidney cells. Then she poked the cells with a blunt glass probe, or sucked up a bit of the cell membrane into a tiny pipet to stretch it. This pushing or tugging at the plasma membrane would, presumably, relay a signal to any mechanosensors within that membrane. While perturbing the cells, she measured any influx of ions across their membranes.
Sure enough, the cells expressing OSCAs responded strongly to the pokes and pinches, letting ions in after a deformation of as little as six microns. Among four clades of OSCAs found in plants, members of three responded to Murthy’s prodding or stretching. (It’s still possible the fourth clade contains mechanosensors that didn’t work the same way in the kidney cells, or that required a stronger poke than Murthy gave.)
Did the OSCAs work alone, or did they rely on other parts of the cell to sense membrane tension? To find out, Murthy purified the OSCA1.2 protein and inserted it into membranous bubbles devoid of any other cellular components. Again, the mechanosensor created a current when she stretched the membranes. “These are actually bona fide pore-forming ion channels that sense mechanical force,” Murthy concludes.
Next, the researchers turned to animal proteins in the TMEM63 family, OSCA’s far-flung cousins. Murthy tested TMEM63 proteins from fruit flies, mice, and people, and many responded to a pinch. The presence of similar proteins doing the same job in plants and animals suggests the OSCAs and TMEM63 channels belong to an ancient and important family of mechanosensors, says Murthy.
Her work complements and confirms another recent study, by researchers at Peking University in Beijing, which also reported that two OSCA family members respond to mechanical sensation. In that study, and another in eLife also by Patapoutian’s group at Scripps, scientists determined the structure of OSCA family members, which form a double-barreled channel in cell membranes.
“All of these papers taken together seal the deal—this is definitely a family of mechanosensitive channels,” says Elizabeth Haswell, a plant biologist at Washington University in St. Louis who was not involved in any of these recent studies. “It makes a great foundation for the next set of experiments.” She’s curious what happens in plant cells after OSCAs open, and how their activity might explain the stunted growth that happens in plants without them.
Murthy and Patapoutian, meanwhile, look forward to studying how exactly OSCA and TMEM63 open when the membranes move, and where in the mammal body different TMEM63 proteins are expressed. Murthy also expects researchers will find diseases that result from deficiencies in TMEM63.