In 2010, Patapoutian of the Scripps Institute and his colleagues discovered proteins that act as two switches—proteins called Piezo1 and Piezo2 (a mechanically sensitive ion channel). Recently, Patapoutian shared the Nobel Prize with David Julius, who discovered how the feeling of heat and cold can be perceived.
A mechanosensitive ion channel is an ion channel that can sense changes in the mechanical force of the cell membrane and react quickly. This reaction of the ion channel can convert the mechanical signal sensed by the membrane into an electrical signal or a chemical signal. Mechanosensory is closely related to life activities, and its related research was first carried out in Escherichia coli. Through the study of the mechanically sensitive ion channel MSCs protein family in Escherichia coli, it has been clearly explained how bacteria respond to changes in mechanical forces such as osmotic pressure to maintain life activities. Subsequently, the researchers conducted studies on the NOMPC in Drosophila and the DEG/ENaC channel family in nematodes, which explained relatively clearly the molecular basis of response to mechanical forces in lower eukaryotes. However, the molecular basis for the production of touch, proprioception, and hearing in mammals in response to mechanical forces has always been unclear. Scientists speculate that there is a certain protein that may act as both a force sensor and an ion channel, which can react and conduct mechanical force signal in nearly microseconds. But what exactly are these combined receptor-channel proteins?
To this end, Patapoutian and his colleague Bertrand Coste developed a research plan. They used a special mouse cell that can be converted into a measurable current for monitoring when tapped with a pipette. Then, they used gene knockout methods to screen candidate ion channel genes, by observing which batch of cells suddenly lost their tactile sensitivity, and then identifying their related genes. After a year of hard work, until 2010, Dr. Ardem Patapoutian’s research group identified the Piezo protein family for the first time, which is the first truly mechanically sensitive non-selective cation channel in mammals. This discovery was considered It is a landmark discovery to understand the important life activity of mechanical force in mammals.
Piezo ion channels are one of the mechanically sensitive ion channels. They are selectively permeable to Na+, K+, Ca2+ and Mg2+. The channel family contains two structurally and genetically similar proteins, Piezo1 and Piezo2, both of which are activated by stress. Through the study of the molecular structure of this family, it is found that the members of the piezo family are large protein substances with more than 2,000 residues, which cross the membrane about 30-40 times. They can be said to be the most transmembrane molecules known to man. The molecular weights are 55kDa and 70kDa, respectively. Later, the scientists analyzed the spatial structure of the piezo protein by cryo-electron microscopy, and the images obtained were very amazing. The three Piezo proteins form trimers across the cell membrane. With the central hole as the center, the three proteins spiral outward to form a spatial structure similar to that of a propeller blade. They bend upwards and outwards, forming a deep depression on the surface of the cell. Based on its spatial structure, scientists predict that there are two possible mechanosensory mechanisms. One is that when a mechanical force acts on the cell membrane, the “leaf” structure will drive the “support rod” structure inside the cell membrane, thereby opening the central hole for ion flow; another speculation is that the way Piezo’s “leaf” structure makes the cell membrane pleated may suggest a different mechanism: whether it is pushed or pulled, it will increase the cell membrane tension, and the curved channel may be flattened and opened.