Researchers reveal shape of glutamate transporter

In a new study, researchers from the University of Sydney in Australia and the University of Illinois at Urbana – Champaign in the United States reveal one of the most important molecular machines in our cells – the glutamate transporter – — shape, which helps explain how our brain cells communicate with each other. Relevant research results were published online in the journal Nature on titled is The February paper 17, 2021. ” Glutamate transporters have a chloride channel with two hydrophobic gates” .

Glutamate transporters are tiny proteins on the surface of all our cells that turn chemical signals on and off, playing an important role in ensuring that all cell-to-cell conversations run smoothly. They are also involved in neural signal transduction, metabolism, and learning and memory.

The researchers used cryo-electron microscopy (cryo-EM) embedded in the cell membrane to capture the structure of glutamate transporters in great detail, showing that they look like ” twisted elevators ” .

This discovery, a world first, opens up a whole new realm of possibilities: investigating whether defects in glutamate transporters may be the cause behind neurological diseases such as Alzheimer’s disease.

, co-first author of the paper and Ichia Chen a PhD student at the University of Sydney, said, ” I was surprised when I first saw this image. It reveals how the glutamate transporter works and explains years of previous research. ”

Multitasking glutamate transporter

The researchers by using cryo-EM to analyze thousands of images trapped in a thin layer of ice . were able to ” photograph ” the structure of the glutamate transporter

cryo-EM is a highly sensitive microscope that made this research possible. It uses electron beams to photograph biological molecules, making visible what is invisible to the naked eye.

The findings also confirm what scientists have suspected for some time: that glutamate transporters are multitaskers. , co-corresponding author of the paper and from the School of Medicine and Health at the University of Sydney, Professor Renae Ryan said, ” Using cryo-EM , we have uncovered for the first time how the glutamate transporter multi-tasks – performing dual functions, i.e., in the cell membrane. move chemicals ( such as glutamate ) up , while also allowing water and chloride ions to pass through at the same time. These molecular machines use a very twisted elevator-like mechanism to move their cargo across the cell membrane. But they have an extra Function: They allow water and chloride ions to cross cell membranes. We have been studying this dual function for some time, but before now we have never been able to explain how glutamate transporters do this. Utilizing include Using a combination of techniques including cryo-EM and computer simulations, we captured this rare state where we can observe both functions occurring simultaneously. ”

Professor Ryan said, ” Understanding how these molecular machines in our cells function allows us to explain their defects in disease states and also gives us clues about how to target these molecular machines with drugs. ”

Key to bridging deficiencies in disease

Mapping the detailed structure of glutamate transporters is an important tool for understanding how our bodies work and the mechanisms behind some diseases.

Defects in glutamate transporters are associated with many neurological diseases such as Alzheimer’s disease and stroke. This also includes rare disorders such as episodic ataxia , a disorder that affects movement and causes periodic paralysis, caused by the uncontrolled leakage of chloride ions through glutamate transporters in brain cells cause.

, co-first author of the paper, from the University of Sydney Qianyi Wu Dr , said: ” Understanding the structure of the glutamate transporter that controls the normal flow of chloride ions may help to design devices that can ‘ block ‘ this chloride in episodic ataxia. Ion channel drugs. ”

The result of teamwork

by researchers in Australia and the United States The paper is the result of seven years of work . This study also highlights the importance and potential of high-resolution microscopy for understanding biological processes.

, co-corresponding author of the paper from the University of Sydney Josep Font Dr. , said, “ We are really excited to be using the new Glacios at the Sydney Microscopy and Microanalysis Facility at the University of Sydney. cryo-EM . The opportunity to use this microscope ‘ in-house ‘ will accelerate our research and understanding of these important molecular machines. “