Serotonin is a major neurotransmitter, regulating mood, appetite, sleep, memory, learning, and other functions by binding to dedicated receptor proteins<\/strong>. Serotonin receptors have been researched for decades, but details about their structure and function are hard to come by. EPFL scientists have now made the first ever computer simulation of a notoriously elusive serotonin receptor that is involved in fast signal transmission in neurons and plays a central role in disorders such as schizophrenia, chemotherapy nausea, irritable bowel syndrome, anxiety, and seizures. The work is published in the journal Structure<\/em>.<\/p>\n The 5-HT3 receptor (5-HT stands for 5-hydroxytryptamine, the technical name of serotonin) is the third member of a family of serotonin receptors. It is made up of five proteins that form a tube-like channel through the cell membrane. When serotonin binds to the receptor, a gate opens up and allows positively charged ions of sodium, potassium or calcium to flow through the channel<\/strong>. This changes the electrical balance between the inside and outside of the neuron, and an electrical signal is transmitted across the cell membrane.<\/p>\n In our central and peripheral nervous system such “neurotransmitter-gated” receptors with ion channels like 5-HT3 are critical for signaling between neurons. However they have been notoriously difficult to study with traditional tools of structural biology. But in a 2014 Nature<\/em> paper, the lab of Horst Vogel at EPFL published the first ever, high-resolution and complete 3D structure of the 5-HT3 receptor.<\/p>\n Now, Vogel’s lab has followed up with a complete computer simulation of 5-HT3 that reveals the motions of each atom across microseconds and at atomic, sub-nanometer resolution. This so-called “molecular dynamics simulation” uses the structure of 5-HT3 receptor that Vogel’s lab uncovered in 2014 to accurately depict the structural changes that 5-HT3 undergoes inside a cell membrane after serotonin binds and activates it to open its ion channel<\/strong>. To make sure that they were not looking at random structural changes of the receptor itself, the researchers also ran simulations of the receptor without the ligand.<\/p>\n “Our 2014 paper delivered the architecture of the 5-HT3 neuroreceptor with atomic detail,” says Horst Vogel. “But that was a static structure that did not explain how the receptor functions as a gated transmembrane ion channel to transmit electrical signals across the cell membrane.”<\/p>\n Specifically, Vogel’s team wanted to know how a ligand, e.g. serotonin, that binds to the part of 5-HT3 outside of the cell, can open the ion channel’s gate<\/strong>, which is buried inside the cell’s membrane six nanometers away — a considerable distance in the world of molecules.<\/p>\n With this degree of accuracy, the researchers feel confident that the simulation delivers a realistic description of how the 5-HT3 receptor works. Beyond that, it also acts as a blueprint for the function of neurotransmitter-gated, ion-channel receptors in general.<\/p>\n “The data can help us understand how neuronal signals are transmitted at an atomic scale<\/strong>,” says Vogel. “This would hold enormous potential for future drug development and treatment of disorders linked to these receptors, including schizophrenia, anxiety, nausea, and others.”<\/p>\n<\/div>\n<\/blockquote>\n","protected":false},"excerpt":{"rendered":" From the Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne\u00a0media release: EPFL scientists have elucidated for the first time how a notoriously elusive serotonin receptor functions with atom-level detail. The receptor transmits electrical… Read more »<\/a><\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[5,319,4,6,43],"tags":[135,42,127,25,19,49,31,158,363,12,431,362,62],"_links":{"self":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/19024"}],"collection":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/comments?post=19024"}],"version-history":[{"count":1,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/19024\/revisions"}],"predecessor-version":[{"id":19031,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/19024\/revisions\/19031"}],"wp:attachment":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/media?parent=19024"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/categories?post=19024"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/tags?post=19024"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"brain](\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2013\/02\/brain_scan.jpg\")
EPFL scientists have elucidated for the first time how a notoriously elusive serotonin receptor functions with atom-level detail<\/strong>. The receptor transmits electrical signals in neurons and is involved in various disorders, meaning that the discovery opens the way for new treatments.<\/p>\n