Mechanism of action of VMAT2 in neurons. Courtesy of the Institute of Physics, Chinese Academy of Sciences.
Happiness can be abstract and poetic, a beautiful melody, a splendid flower, a praise of life. Happiness can also be concrete and rational, being neurotransmitters such as dopamine, serotonin, and endorphins that are transmitted between tens of billions of neurons in the brain. Beware, if the neurotransmitter serotonin isn't evenly distributed, the pleasure may slip away.
This is the relationship between the brain and emotions. Many people may be surprised when they first understand this - it is hard to imagine that human emotions can be so functional, so "controllable", that they can be interpreted and summarized in the same way that they can explain how a computer works.
Not long ago, Jiang Daohua's team from the Institute of Physics of the Chinese Academy of Sciences, the Beijing National Research Center for Condensed Matter Physics, and the team of Zhao Yan from the Institute of Biophysics, Chinese Academy of Sciences, reconstructed the high-resolution structure of the vesicle monoamine transporter VMAT2 in different conformations through cryo-electron microscopy single particle technology, and explained in detail how VMAT2 transports monoamine neurotransmitters into vesicles. The research results were published in the international academic journal Nature with the title of "Transporting and Inhibiting Mechanism of Human VMAT2".
VMAT2 is the most important vesicle monoamine transporter in the brain, responsible for transporting neurotransmitters such as serotonin, dopamine, epinephrine, norepinephrine, and histamine to the vesicles for storage in order to release monoamine neurotransmitters upon external stimuli.
What happens in the brain when people are so irritable that they can't hear a sound, or they're depressed all night, or when they suddenly have a crush on a face?As the mystery of neurotransmitters is revealed, we can finally figure out how the brain tells you to be happy.
In fact, scientists are always trying to read emotions. In 1921, German pharmacologist Otto Leuivy designed the double-frog heart perfusion experiment, which proved the existence of neurotransmitters for the first time. He stimulated the first frog to excite its vagus nerve, and immediately observed that the frog heart was suppressed, and Leuvy injected the perfusate of the first frog's heart into the second frog's heart, and then he noticed that the second frog's heart was also inhibited!
Leuvi later discovered that the stimulated vagus nerve was not emitting electrical signals, but a chemical. He separates this substance, which is acetylcholine. This substance was identified by Henry Dale in 1929 as a normal component of the animal's body. Together with Dale, Leuvy won the Nobel Prize in Physiology or Medicine in 1936.
Although it is the first neurotransmitter to be discovered in human history, acetylcholine is not very well-known among the public, far less than its "Internet celebrity brothers" dopamine and adrenaline. Dopamine was discovered by Swedish scientist Alvid Carlson, who was awarded the 2000 Nobel Prize in Physiology or Medicine along with two other scientists who explain synaptic transmission, for demonstrating that insufficient dopamine secretion can even trigger Parkinson's disease.
What Tom Maniadis, a professor of molecular biology at Columbia University in the United States, wants to figure out is how neurons recognize each other without messing around with the transmission of neurotransmitters. He discovered a gene cluster called protocadherin, which is the key to mental illnesses such as depression, bipolar disorder, psychosis, and autism.
Today, the research of Jiang Daohua's team and Zhao Yan's team has promoted the study of VMAT2 transporter monoamine. It provides an important structural basis for understanding the molecular mechanisms of VMAT2, such as substrate recognition, drug inhibition, and proton coupling transport process, and also provides template information for the development of better drug molecules.
The analytical method used in this study is not only applicable to VMAT2, but can also be applied to other small membrane proteins. This has a positive effect on the structural elucidation of membrane transporters and other small proteins.
The pace of scientific research will not stop, and the research team intends to continue to dig deeper into the "secrets" of VMAT2. For example, VMAT2 can identify a variety of endogenous and exogenous substrates, and is there a common transport mechanism between them?How do protons participate in and drive protein conformational conversion during transport?
Before learning to breathe, the fetus's brain has already begun to build a "neuronal highway", a complex neural network from scratch, and a large number of neurotransmitters are stored in vesicles. The beginning of life is not only the most shocking art in the world, but also the most sophisticated procedure. Although we have an extremely efficient and sophisticated neural network, perhaps humanity still has a long way to go if we want to figure out how it works.
It's long, but it's worth it.
China Youth Daily, China Youth Network reporter Zhang Miao **China Youth Daily.
*: China Youth Daily.