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    Home > Biochemistry News > Biotechnology News > Nature: Widespread brain receptor hides surprising mechanism of action

    Nature: Widespread brain receptor hides surprising mechanism of action

    • Last Update: 2022-05-17
    • Source: Internet
    • Author: User
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    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
    Glutamate binds to receptors on brain cells, opening a channel into the cell, allowing ions to pass through, propagating electrical signals


    "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.
    Ski said


    Each receptor can bind up to four molecules of glutamate and produce four different levels of conductivity
    Previous studies linked binding to conductivity in a simple step-by-step fashion, with each additional glutamate molecule bound, the conductivity increased further


    While this explanation makes sense, no one has looked closely to confirm it
    In the new work, the researchers combined cryo-electron microscopy techniques and sophisticated data analysis to reveal, for the first time, a detailed picture of glutamate binding to the receptor


    "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
    This overturns the commonly held belief that each subunit binds glutamate individually, and points to the complexity of neuronal signaling and drug responses


    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
    Furthermore, the conductivity level of a receptor is not directly related to the amount of glutamate bound to it; a receptor can have two or more glutamate and still only reach first-order conductivity levels


    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
    Knowing more about the specific activation state of glutamate receptors may help develop better drugs to treat glutamate receptor-related disorders such as depression, dementia, Parkinson's, epilepsy and stroke


    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.
      Yelshanskaya, Dhilon S.
      Patel, Christopher M.
      Kottke, Maria G.
      Kurnikova, Alexander I.
      Opening of glutamate receptor channel to subconductance levels .
      Nature , 2022; DOI: 10.

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