Nature: Widespread brain receptor hides surprising mechanism of action

The findings, published April 20 in the journal Nature, may aid the development of a new generation of more effective neurological and psychiatric treatments with fewer side effects

The new study took a deep dive into the brain's most prevalent neurotransmitter, glutamate

"The way the brain works is through communication between neurons, and these are the main receptors that allow this communication," said Alexander Sobolev, associate professor of biochemistry and molecular biophysics at Columbia University and senior author of the paper.

Each receptor can bind up to four molecules of glutamate and produce four different levels of conductivity

While this explanation makes sense, no one has looked closely to confirm it

"We actually ran the experiments under conditions where we saw all these intermediates, one glutamate, two glutamate, three glutamate, and then all four bound in," Sobolevski said.

These images show that glutamate only binds to subunits of the receptor in a specific way

Rather than a direct step-by-step transition, Sobolevsky and his colleagues found that the glutamate molecule must first bind to one of two specific subunits of the receptor before it can bind to the other two

This result opens up a whole new avenue of research, and the team is now exploring how different accessory molecules on neurons affect this interaction

Video: https://youtu.

This research was supported by the National Institutes of Health (R01 CA206573, R01 NS083660, R01 NS107253, R01 AR078814, R01 GM128195, and R01 AG065594) and the National Science Foundation (1818086, 1818213, and 1563291)

Journal Reference :

1. Maria V.